PICU Doc On Call

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

Welcome to our Episode about a 4-year-old girl with a chief complaint of headache and vomiting

Here's the case:

A 4-year-old presents to the PICU with headaches + vomiting and abnormal CT scan findings. The patient presented to the ED with h/o abdominal pain X 5 days with nonbilious, non-bloody emesis. Initial CBC, UA was normal. The patient was given some pain meds and IV fluids. Further history revealed that the patient has been having severe headaches for the last 5 days and had emesis secondary to the headaches resulting in generalized, non-specific abdominal pain. No h/o of trauma or seizures, no h/o of fever or diarrhea, no h/o toxic ingestions h/o recent travel, exposure to sick contacts, COVID test negative. No family h/o migraines, her immunizations are UTD. Besides the normal UA and CBC, her CMP was also normal.

A CT scan of the head revealed right frontoparietal mass with moderate surrounding edema, 6 mm leftward midline shift, diffuse sulcal narrowing, and right cisternal narrowing. Imaging of the abdomen (US and CT w/ contrast) was unremarkable. An MRI done revealed: Right parietal diffusion restricting lesion, most compatible with abscess. Moderate surrounding vasogenic edema. Given her abdominal pain- Abdominal KUB as well as contrast CT scan of abdomen and pelvis were performed and revealed no abdominopelvic pathology.

In the ED her vitals were normal and the patient was afebrile. On her PE: the patient appeared sleepy but woke up and answered questions appropriately. No focal deficits, PERRL, normal tone and strength. The rest of her physical exam was completely normal. She now is transferred to the PICU for serial neurological exams.

To summarize key elements from this case, this patient has:

• Headache with altered mental status
• No focal deficits
• Vomiting
• surprisingly no fever
• Imaging showing right frontoparietal mass.
• All of which brings up a concern for brain abscess
• This episode will be organized…
• Epidemiology and pathogenesis
• Diagnosis
• Management

Rahul, can you inform our listeners about the epidemiology of brain abscesses?

Only about 25% of brain abscesses occur in children. Incidence in developed countries is about 1-2% while in developing countries it's about 8%. Peak incidence in children is seen between the ages of 4-7 years and is more common in males. Brain abscess in the neonatal age group is rare but are associated with a higher risk of complications and mortality.

Risk factors for brain abscess include Otologic infections (ear, sinus, and dental infections), Congenital heart disease (30% of patients with BA have an underlying heart defect) with intra-cardiac or intrapulmonary shunting (pulmonary AV malformations in hemorrhagic telangiectasis), immunodeficiencies (solid organ transplantation, HIV, etc), prolonged steroid use, diabetes, alcoholism neurosurgical procedures, trauma. Other rare causes can be airway foreign bodies, congenital dermal sinuses, and esophageal procedures (such as dilatations).

Brain abscess typically begins with a localized area of cerebritis which evolves through various stages (typically 10-14 days) to develop into an encapsulated collection of purulent material with peripheral gliosis or fibrosis.

40-50% of the spread of infection is via a contiguous site of infection such as otitis, sinusitis or mastoiditis or from head trauma or neurosurgical procedure. 30-40% is spread through the hematogenous route from endocarditis, pulmonary infections, or dental abscess.

90% of brain abscesses in children are supratentorial. Mastoiditis, sphenoidal sinusitis, otitis media results in BA in the temporal lobe or cerebellum. Frontal lobe BA are due to frontal or ethmoid sinusitis or dental infections. BA from hematogenous spread results in multiple abscesses and typically follows the distribution of the middle cerebral artery including parietal and occipital lobes.

Rahul, what are some of the common pathogens seen in brain abscesses?

A meta-analysis reported the most common organisms in children with BA. These include streptococcus species seen in 36% (seen mostly with otologic infections, and strep viridans with endocarditis) followed by staphylococcal sp seen in 18% (head trauma, surgery, or skin infections) and gram-negative enteric bacteria seen in 16% (Proteus, Klebsiella, E. coli and Enterobacteriae. Citrobacter, E Coli, or proteus species are seen in neonates.

BAs from opportunistic microorganisms are usually multiple. They can occur in HIV-positive children with a low CD4 count; the most common pathogens are Toxoplasma, Nocardia, and Mycobacterium spp. Fungal abscesses (mainly Aspergillus or Candida) typically affect solid organ transplants recipients or children treated for leukemia

To summarize, altered mental status in a patient who is immunocompromised, think of opportunistic infections. Remember these patients can present even without a fever!

Rahul, what are some of the typical clinical features seen in patients with a brain abscess?

Clinical features would depend on site, size, involvement of surrounding area, patient’s immune status, and organisms involved. Fever with headache is typical. Vomiting is usually associated with headaches. Neurological manifestations include-Seizures, hemiplegia, cranial nerve palsies, and altered level of consciousness ranging from drowsiness to coma. Neonates can have bulging fontanelle and even increased head circumference.

The classic triad of fever +headache +neurological deficits is clinically seen in a small percentage (~33%) of patients. Frontal abscesses may remain asymptomatic especially if they are small. Pott's Puffy tumor also called Pott's edematous tumor (PET), is a sub-periosteal abscess of the frontal bone, associated with osteomyelitis of the frontal bone. which can give rise to BA. Meningeal signs are seen in 25% of patients with BA.

To summarize, Pott puffy tumor is osteomyelitis of the frontal bone with associated subperiosteal abscess causing swelling and edema over the forehead and scalp. It is a complication of frontal sinusitis or trauma.

If you had to work up this patient with a brain abscess what would be your diagnostic approach?

• I would start with a CBC with diff, Blood Cx, ESR, CRP, and CMP. Such tests are abnormal in only 20% of pediatric patients with BA.
• After CT or MRI, an LP can be attempted. LP would be contraindicated if there is a non-communicating obstructive hydrocephalous and brain shift. CSF fluid analysis, gm stain, and cultures could be helpful to find an organism and tailor therapy. Although CSF studies can be normal in 30% of patients with a BA. The sudden worsening of a preexisting headache can indicate a rupture of the brain abscess into the ventricular space or impending herniation from the lesion’s mass effect. Significant alteration in mental status is an ominous clinical finding. Abscesses located within their brainstem typically present with fever, headaches, hemiparesis, and focal cranial nerve findings involving CN III, CN VI, and CN VII.

• MRI is considered as the gold standard (low radiation risk, better resolution, and lower toxicity of contrast compared to CT). MR imaging may require sedation and take a longer time compared to CT (which is readily available and may not require sedation due to the speed of image acquisition and can be performed quickly prior to an LP). MR has higher sensitivity and specificity in the differential diagnosis with cystic or neoplastic lesions. An MR study for bacterial BA will show a necrotic center with the low signal at the DW-MR (diffusion-weighted magnetic resonance) and a T2-hypointensity with enhancement for the peripheral capsule. Fungal abscesses show a hypointense center in the T2-weighed image with variable expression in DW-MR.
• CT may reveal a mass lesion but MRI will help confirm the diagnosis and characterize the abscess better. Pus obtained from the aspiration or biopsy during the operating room can be used for culture.
• Cultures (for aerobic and anaerobic bacteria, Mycobacterium, fungi, protozoa), Gram, and special stains (for fungi, Mycobacterium, Nocardia) and polymerase chain reaction should be performed on blood, CSF, and pus of the cerebral abscess. It is best to involve our ID colleagues in a patient with BA to guide diagnostic studies as well as therapies. The culture positivity of blood and CSF samples is low (22-28% of cases). The rate of micro-organism isolation from abscess samples is about 60–80%, with polymicrobial involvement in about 20–30% of cases.
• Other studies can be obtained on a case-by-case basis depending on the primary focus would include an echocardiogram, CXR, abdominal US or CT, and bone imaging.
• Besides infectious disease and NS experts, consults with cardiology, hematology, OMFS, and ENT experts may be required.

To summarize, your approach to brain abscesses involves imaging, isolation of the lesion, and fluid/tissue diagnosis. Diagnostics such as an echo may reveal a primary source. This is definitely a coordinated effort with ID, neurosurgery, as well as neurology. These patients may also require prophylactic anti-epileptics peri-biopsy.

If our history, physical, and diagnostic investigation led us to brain abscess as our diagnosis what would be your general management of framework?

As we have mentioned before, A multidisciplinary team approach involving the PCCM, NS, ID, radiologists, and pharmacists are required for the successful management of patients with BA in the PICU.

Again, good basic PICU care with close attention to airway patency, adequacy of oxygenation/ventilation as well as stability of hemodynamics should be the first line approach in such patients admitted to the PICU. Good access for medication administration may include the need for a PICC line. Attention to neuro-status by frequent physical exams including attention to the patient's handling of oral secretions should be a priority. Continuous EEG may be required depending on the site, size, and involvement of the surrounding area.

Long-term antibiotics are the mainstay of therapy: A combination of vancomycin+ceftriaxone and metronidazole for 4-6 weeks if surgically drained vs 8 weeks for those without surgical drainage. Along the same lines, it is important to anticipate PICC lines or stable central lines for the long-term abx therapy.

Non-operative approach can be considered in patient with multiple small abscess or a single abscess which is < 2.5cm. Non surgical approach is also considered in patients with surgically inaccessible lesions, early cerebritis, or medical comorbidities that puts patient at high surgical risk.

What about operative approach?

Operative approach involves aspiration (typically CT guided), or excision. Aspiration results in removal of infected nidus (source control) as well as provision of material for gm stain/Cx. Excision of the abscess cavity may be useful when it is located in a periventricular or posterior fossa distribution, is loculated, or contains a foreign body. Excision should also be considered for abscesses that enlarge after 2 weeks of antibiotic therapy or that fail to shrink after 3 to 4 weeks of antibiotics. Primary excision may be the procedure of choice for lesions located in the cerebellum. Compared to aspiration, excision of BA in nonvital areas of brain had a lower rate of re-operation, a higher rate of postoperative abscess clearance, and better neurologic improvement after 1 month with no difference in long-term neurological outcomes or mortality.

Rahul, what are some of the prognostic features of BA?

BA from a contiguous focus of infection and those developing after a traumatic injury tend to have a better prognosis. Poorer prognosis is associated with delayed diagnosis, immunocompromised status, rupture of the abscess into the ventricular space, fungal etiology, and pretreatment neurologic compromise.

Let’s summarize

1. The classic triad of diagnosis of BA- headache +fever+ neurological deficit is seen in only 1/3rd of the patients with BA. Therefore a high index of suspicion is required based on patients risk factors such as immunosuppression, cyanotic heart disease etc.
2. Early imaging with CT/MRI is necessary to diagnosis
3. Antibiotic therapy should not be delayed. Triple therapy with vancomycin +ceftriaxone and metronidazole is typically initiated at diagnosis.

This concludes our episode on brain abscesses. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

References

• Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 67 Central nervous system infections and related conditions (Havlin KM et al.)
• Reference 1: Mameli, C., Genoni, T., Madia, C. et al. Brain abscess in pediatric age: a review. Childs Nerv Syst 35, 1117–1128 (2019).
• Reference 2: Panda PK, Natarajan V, Vigneshwar NKV, Sharawat IK. Clinical Presentation and Outcome of Children with Brain Abscess. Ann Indian Acad Neurol. 2021 Nov-Dec;24(6):951-952. doi: 10.4103/aian.AIAN_794_20. Epub 2021 Jan 19. PMID: 35359509; PMCID: PMC8965945.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

and I'm Rahul Damania from Cleveland Clinic Children’s Hospital and we are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

Welcome to our Episode an 18 -year old with sore throat, and unilateral L-sided neck pain for ~2 weeks.

Here's the case presented by Rahul:

An 18-year-old female presents to the ED with cough, fever, fatigue, sore throat, and unilateral L-sided neck pain for ~2 weeks. The patient also has been having non-specific chest pain, weight loss, and decreased appetite for ~ 1 month.

Patient has no recent travel h/o, no h/o of vaping or illicit drug use, and there were no sick contacts at home. Vitals revealed an HR 105, BP 116/66, Temp 38.3, and respiratory rate 35, She was 65 Kg and SPO2 on 2L NC was 100%. Physical exam was negative except (L) neck tender to palpation. There was no goiter, lymphadenopathy or hepatosplenomegaly.

An initial chest x-ray was significant for possible multi-lobar pneumonia versus metastases. A Chest CT revealed multifocal septic emboli in the lungs. Echo did not show any gross vegetation. She has no rash or any trauma to the neck or difficulty swallowing, no oral ulcers, joint pain, or diarrhea. She had no recent dental work or drinking of unpasteurized milk or eating raw fish or meat. She was admitted to the PICU as she had hypotension requiring fluid boluses, and lab works significant for hyponatremia, rhabdomyolysis, worsening AKI, elevated ferritin, and elevated D-dimer. Her serum uric acid was 9.9, LDH = 230 (normal) ,ESR 78 (normal = 20 or less). Her serum lactate and serum troponin and BNP were all normal. Pertinently, US neck revealed an occlusive thrombus in the (L) IJ vein (done so as to avoid contrast in face of AKI), and blood cultures sent.

To summarize key elements from this case, this 18-year-old female presents with

• fever +cough+sore throat
• Fatigue + Weight loss
• (L) neck pain
• Hypotension with abnormal labs including a concerning WBC with (L) shift, anemia, AKI, elevated uric acid, and ESR
• Chest CT with possible pulmonary emboli
• US showing occlusion.
• All of which brings up a concern for possible malignancy or pulmonary emboli from a septic focus in the neck and a possible diagnosis of Lemierre syndrome
• This episode will be organized…
• Definition
• Diagnosis (physical, laboratory)
• Management
• Rahul: What is the definition of Lemierre’s syndrome?
• Lemierre’s syndrome, also known as post-anginal septicemia or necrobacillosis, is characterized by bacteremia, internal jugular vein thrombophlebitis, and metastatic septic emboli secondary to acute pharyngeal infections. All of which are seen in our above case presentation. Previously called as the forgotten disease as its incidence was decreasing due to the increasing use of antibiotics especially penicillin for URI. However, recently there is an increase in Lemierre’s disease cases with decreased use of antibiotics due to antibiotic stewardship. The recent increase in Lemierre disease due to decreased antibiotic use has not been proven and remain controversial.
• Rahul what are some of the causative organisms of Lemierre syndrome?
• The most common causative agent of Lemierre’s syndrome is Fusobacterium necrophorum, followed by Fusobacterium nucleatum and anaerobic bacteria such as streptococci, staphylococci, and Klebsiella pneumoniae.
• Rahul: Can you tell our listeners about the pathophysiology of Lemierre’s syndrome?
• Lemierre syndrome can occur in health adults (more common in males in the age group of 14-24 years). Risk factors include immunocompromised patients, organisms, and environmental conditions. Lipopolysaccharides in F. necrophorum have endotoxic properties and are important virulence factors. The causative bacteria invade the pharyngeal mucosa previously weakened by preceding viral or bacterial pharyngitis, and lateral pharyngeal space, resulting in subsequent internal jugular vein septic thrombophlebitis and metastatic infections.
• Pneumonia or pleural empyema is the most common metastatic infection in Lemierre’s syndrome. Septic syndrome co-occurring with ear, neck and pulmonary empyema is a rare emerging medical condition. Proposed routes of infection are direct invasion and lymphatic or hematogenous spread to the connective tissue and associated clinical abscess formation or distant septic embolic metastasis.
• Once infection has reached the IJV, hematogenous spread to other sites can occur, causing various complications and ultimately death due to septic shock if antibiotics are delayed.
• The lungs are most commonly affected in up to 85% of cases. Lung lesions commonly appear as necrotic cavitary lesions but can also present as infiltrates, pleural effusions, empyema, lung abscesses, and necrotizing mediastinitis. Epidural and brain abscesses have been as complications of Lemierre’s syndrome and presumably result from the retrograde intracranial extension of IJV thrombosis. Less common infections include: soft tissue abscesses, pyomyositis, splenic and liver abscesses, osteomyelitis, endocarditis, pericarditis, renal abscess, and brain abscess.
• Atypical Lemierre’s syndrome involves thrombophlebitis of vessels other than the IJ. It may also involve bacteria other than Fusobacterium necrophorum or F. nucleatum.
• To summarize, In Lemierre syndrome the disease course is usually rapid and irreversible; therefore, timely diagnosis and prompt antibiotic therapy is important. Lemierre syndrome must be suspected in any patient with acute tonsillo-pharyngitis with persistent neck pain and septic syndrome. Septic pelvic thrombophlebitis complicated by multiple septic emboli after intrauterine device insertion has been reported in adults.

Pradip: What are some of the clinical manifestations of Lemierre Syndrome?

In any patient deep neck infections, subsequent septicemia, thrombophlebitis of the IJV, and metastatic infections (ascending or descending septic emboli) should arouse suspicion for Lemierre's syndrome. In any ill-appearing patient with acute tonsillopharyngitis (throat pain, dysphagia, productive cough) with high fevers, malaise, and neck pain with tenderness should lead to the suspicion of Lemierres syndrome. Patients can also develop trismus. Most young people present with pharyngitis initially, but the old-aged group present with distant complications, such as empyema or brain abscess. Persistent headache with focal neurological signs should alert the clinician of Sagittal sinus venous thrombosis, brain abscess or meningitis.

If you had to work up this patient with Lemierre syndrome what would be your diagnostic approach?

• A good history and physical exam is very important. Any ill-appearing patient with sore throat, high fever, neck pain +tenderness should prompt further evaluation of Lemierre syndrome.
• CBC with differential, blood cultures (aerobic and anaerobic), CRP, CMP, DIC panel should be sent.
• Contrast-enhanced computed tomography (CT) of the neck is the imaging of choice as it detects vascular thrombosis of the IJV and other complications such as pulmonary emboli, empyema, osteomyelitis, and brain or epidural abscess. CT shows intra-luminal filling defects, thrombosis, and enhancement of the IJV along with soft tissue swelling.
• Doppler ultrasonography although less sensitive than CT can be used especially if contrast cannot be used due to AKI (as in our case above). US will show an echogenic region within a dilated IJV or a complex mass of cystic and solid components. US can also detect clots in blood vessels. Magnetic resonance imaging has been used in specific cases to detect IJV thrombosis especially when CNS complication such as brain abscess is suspected.
• An echocardiogram would be helpful to evaluate for intra-cardiac vegetations given septic emboli in the lungs were seen in our patient.

If our history, physical, and diagnostic investigation led us to Lemierre syndrome as our diagnosis what would be your general management of framework?

• The ill-appearing patient should be admitted to the PICU as the patient will require prompt attention to airway, breathing, and hemodynamics. Adequate IV access should be obtained as these patients can become hemodynamically unstable from sepsis.
• A multidisciplinary team approach involving the PCCM, infectious disease, hematologists, and ENT physicians is warranted. After appropriate cultures are obtained - Metronidazole and beta-lactamase inhibiting agents like piperacillin-tazobactam. Ceftriaxone or a carbapenem. Metronidazole is bactericidal; it shows excellent penetration into most tissues including the cerebrospinal fluid.
• If IJV suppuration is due to an infected CVL and not a complication of pharyngitis- consideration should be given to the initiation of vancomycin.
• Antibiotic therapy should be continued for at least 3-6 weeks. Once the infection is controlled, therapy can be completed orally. The initial clinical response may be slow as Lemierre syndrome is an endovascular infection and antibiotics may have difficulty penetrating the fibrin clot. Pleural effusion or abscess drainage may be required in selected cases.
• Another important aspect of therapy is the use of anticoagulant therapy with heparin. Anticoagulation plays a part in preventing septic embolic events originating from IJV thrombosis. We typically start low molecular weight heparin such as Lovenox 1mg/kg sc BID with a goal heparin assay of 0.5-1 (done 4 hours after 2nd or 3rd dose). Lovenox dose needs adjustment in AKI.
• Fusobacterium necrophorum is intrinsically resistant to macrolides, fluoroquinolones, tetracyclines, and aminoglycosides. Fusobacterium necrophorum is resistant to Pn G due to the production of penicillinase.

Rahul, what are some clinical pearls or pitfalls to avoid?

• Suspect Lemierre syndrome in any ill-appearing patient presenting with high fevers, sore throat, and neck pain with tenderness.
• Once septic thrombophlebitis has occurred, complications should be evaluated including descending or ascending infections, such as pneumonia, empyema, or brain abscess.
• CT scan of the neck with IV contrast is the study of choice
• Initiate antibiotics early after a blood culture with metronidazole and a beta-lactamase inhibiting antibiotics such as ceftriaxone, piperacillin-tazobactam, or carbapenem such as meropenem
• anticoagulation therapy with low molecular weight heparin should be considered in consultation with hematology.

This concludes our episode on Lemierre syndrome. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

References

• Fuhrman & Zimmerman - Textbook of Pediatric Critical Care Chapter 107: Franzon D et al. Bacterial and Fungal Infections. page 1265
• Reference 1: Lee WS, Jean SS, Chen FL, Hsieh SM, Hsueh PR. Lemierre's syndrome: A forgotten and re-emerging infection. J Microbiol Immunol Infect. 2020 Aug;53(4):513-517. doi: 10.1016/j.jmii.2020.03.027. Epub 2020 Apr 4. PMID: 32303484.
• Reference 2: Walkty A, Embil J. Lemierre's Syndrome. N Engl J Med. 2019 Mar 21;380(12):e16. doi: 10.1056/NEJMicm1808378. PMID: 30893539.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

Welcome to our Episode a 16-year-old who is coughing up blood.

Here's the case:

A 16-year-old female with h/o SLE was transferred to the PICU due to hypoxia requiring increasing FIO2. A few hours prior to admission to the PICU patient also started coughing up blood and had difficulty breathing. The patient was admitted to the general pediatric floor 2 days earlier for pneumonia requiring an IV antibiotic and O2 via NC. Once transferred to the PICU, she had a rapid deterioration with progressive hematemesis, worsening respiratory distress, and saturations in the low 70s requiring escalating FIO2. The patient was emergently intubated using ketamine + fentanyl and rocuronium. Chest radiograph showed: Worsening bibasilar alveolar and interstitial airspace disease concerning pulmonary hemorrhage. The patient was initially placed on HFOV Paw 26, FIO2 70%, Hz 8, Dp 70, and later transitioned to airway pressure release ventilation or APRV. The patient was also started on inhaled tranexamic acid or TXA and high-dose pulse steroids. The patient initially continued to have some blood coming out from the ETT with suctioning but secretions became clear in ~24 hours.

The mother reported that the patient has never had hematemesis/hemoptysis before, or bleeding from any site in the past. Denied history of frequent respiratory infections or recent URI symptoms. The patient has been vaccinated/boosted x3 vs covid. Her COVID PCR is negative. The mother states that she does not engage in tobacco products or alcohol.

A physical exam revealed a well-developed teenage girl laying supine in bed deeply sedated and mechanically ventilated. There was decreased AE at lung bases and coarse breath sounds throughout. There was no hepatosplenomegaly and exams of the heart, abdomen and other systems were normal. There was no skin rash and extremities were well perfused with no clubbing in the fingers. The pulmonary team was consulted and a workup was started for pulmonary hemorrhage.

To summarize key elements from this case, this patient has:

• Autoimmune disease: Systemic lupus erythematosus
• Respiratory Failure warranting MV 2/2 Pulmonary hemorrhage
• Her presentation and deterioration bring up a concern for diffuse alveolar hemorrhage our topic of discussion for today.
• This episode will be organized…
• Definition
• Etiology
• Pathophysiology
• Diagnosis
• Management
• Rahul: How do we define pulmonary hemorrhage (PH):
• PH is defined as the extravasation of blood into airways and/or lung parenchyma. Blood in the airways produces a diffusion barrier resulting in hypoxemia. Due to the reduction of airway diameter from accumulated blood, there is increased airway resistance and even airway obstruction. Subsequently, ventilation can be impaired leading to increased WOB as well as myocardial work required for O2 delivery. Repeated episodes of PH can result in interstitial fibrosis thus changing lung compliance. Hemoptysis by definition is any bleeding from below the vocal cords. PH can be classified as focal or diffuse. Diffuse is further classified as diffuse immune or diffuse nonimmune.

Loss of 10% of a patient’s circulating blood volume into the lungs, regardless of age, causes a significant alteration in cardiorespiratory function and should be considered massive. In adults, massive pulmonary hemorrhage is defined as blood loss of 600mL or more in 24 hours. In infants, the involvement of at least two pulmonary lobes by confluent foci of extravasated RBCs constitutes as massive PH. “Enough bleeding to make one nervous is probably massive.”

Let's pivot and talk about etiologies.

• Pradip, What are some of the causes of pulmonary hemorrhage in the PICU?
• Non-immune diffuse PH is usually seen in patients with congenital heart disease (TAPVR, pulmonary atresia, mitral stenosis, hypoplastic left heart syndrome to name a few) neonates (secondary to sepsis, HIE, BW < 1500 gms, persistent pulmonary hypertension) and due to coagulopathy. bronchiectasis, infections such as TB, mycetomas are also important causes of PH. Cocaineas and vaping (typically adulterated with other substances) are also important toxic causes of DAH.
• Diffuse PH due to immune causes includes pulmonary-renal syndromes (good pastures, Wegener granulomatosis, SLE, anti-phospholipid syndrome PAN, HSP), drug-induced vasculitis (PTU, methimazole, hydralazine, and minocycline) and infections such as hantavirus, CMV, legionella, etc. Lupus and PAN account for the majority of the vasculitis resulting in PH.
• Focal PH: FB aspiration with chronic retention, pulmonary sequestration, AV fistula, thrombus or embolus, and neoplasms.
• Idiopathic pulmonary hemosiderosis a diagnosis of exclusion presents with the triad of hemoptysis, microcytic hypochromic anemia, and diffuse alveolar-filling opacities. Nonspecific lung injury not attributed to vasculitis or immune deposits is noted on microscopic examination.

Alright to summarize diffuse pulmonary hemorrhage — think about non-immune causes secondary to heart disease and immune causes secondary to rheumatologic conditions. Our patient in our case likely had immune-mediated PH.

Let's conclude our episode by going through diagnostics and management.

• If you had to work up this patient with PH, what would be your diagnostic approach?
• We can start with a chest radiograph. Typically in PH, you can see ground-glass diffuse opacities or consolidations; sometimes a mosaic-type perfusion pattern can indicate a true arteriolar vasculitis. In some patients, the chest radiograph can be normal. High Resolution Computed tomography(HRCT) has higher sensitivity and the classic features include ground-glass opacities in a random distribution.
• Bronchoscopy and bronchoalveolar lavage (BAL) are other diagnostic tools. In bronchoalveolar lavage, the pathologist must search for hemosiderin-laden macrophages, which usually appear 24–48 h after the DAH has started. The presence of >5% of hemosiderin-laden macrophages highly suggests the presence of blood from DAH.
• Echocardiogram
• Labs: Blood gas, CMP, CBC, Coagulation panel, ESR, CRP, specific auto-antibodies (consult with renal or rheumatology colleagues). Urine analysis, In some rare cases a biopsy (skin, lung, or kidney) may be needed in pulmonary-renal syndromes.

I would also highly recommend a collaborative approach with pulmonary specialists, rheumatologists, intensivists, and hematology.

• If our history, physical, and diagnostic investigation led us to PH as our diagnosis what would be your general management framework?
• Initially, we must focus on basic PICU care with maintenance of airway and oxygenation/ventilation as well as hemodynamic stability. O2 supplementation EVEN mechanical ventilation may be required; Prior to intubation placement of the patient in Trendelenburg position (which helps clots exit the airway) may be helpful. PEEP should be increased on conventional ventilation for tamponade effect as well as help with hypoxemia. We typically use HFOV with deep sedation +/- chemical paralysis or APRV mode on a conventional ventilator. It is important to correct any coagulation factor deficiency as well as transfuse platelets or pRBCs as needed.
• Increased PEEP, HFOV, and APRV all create increased mean airway pressure which not only has a local tamponade but increases intrathoracic pressure to decrease preload and downstream pulmonary hydrostatic pressure.

What are some other modalities used in DAH?

• Endobronchial tamponade (Fogarty catheter, cuffed endotracheal tube) can be tried if bleeding is restricted to a segment of a particular lung. Right upper lobe bleeding is best managed by intubating the left main stem bronchus with a cuffed endotracheal tube and inflating the cuff of the tube. Utilization of a double-lumen or Carlens-type endotracheal tube may also be helpful in isolating the bleeding segment. Consult with anesthesia colleagues may be helpful in the management of such patients.
• There may be a role for rigid bronchoscopy to identify the source and type of bleeding. Rigid Bronchoscopy can also be used for large volume lavage as well as suctioning of blood and even control the source of bleeding. The help of general or cardiothoracic surgery colleagues is invaluable in such patients. For focal PH- surgical resection of the involved segment or selective embolization of bronchial vessels may be needed.
• What about medical management?
• Specific pulmonary-renal syndromes can be treated using corticosteroids and other immunosuppressive agents. Plasmapheresis is an option for Good Pastures syndrome. High-dose methylprednisolone (30mg/kg or 1gm daily X 3 days followed by slow taper) is typically used in diffuse immune-mediated PH. Cyclophosphamide is the drug of choice for the treatment of patients with Wegener granulomatosis
• Are there any therapeutics on the horizon?
• One study by O’Neil et al in Crit Care Explor 2020 reported the use of Inhaled Tranexamic Acid As a Novel Treatment for Pulmonary Hemorrhage in Critically Ill Pediatric Patients-Cessation of pulmonary hemorrhage was achieved in 18 of 19 patients (95%) with inhaled tranexamic acid with no major adverse events recorded. The study also reported that other variables such as oxygenation and coagulation were not affected by the use of inhaled TXA in our study. Additionally, they reported that the patients received significantly less blood product after receiving inhaled TXA.
• How does TXA work and what are the applications clinically?
• Tranexamic acid (TXA) is a lysine analog that blocks the conversion of plasminogen to plasmin and inhibits binding of plasmin to fibrin which stabilizes the fibrin matrix, thereby reducing bleeding. Systemic TXA, however, may be associated with serious complications including venous thromboembolism, neurotoxicity, and seizures. In our patients, we use inhaled or endotracheally instilled TXA (250-500mg of 100mg/ml solution) every 6 hours. Nebulization is done over 15-20minutes and can be delivered in line during mechanical ventilation. Dosing frequency was subsequently decreased based on patients’ responses.

Rahul, can you summarize today's episode on DAH:

Diffuse alveolar hemorrhage is a medical emergency. 33% can present without hemoptysis. Along with clinical findings of cough, hemoptysis, and dyspnea the presence of hemosiderin-laden macrophages confirms the diagnosis of pulmonary hemorrhage. Protecting the airway and optimizing oxygenation/ventilation is the most important part of management. Then identify and stop the offending agent if possible and administer treatments accordingly.

This concludes our episode on a pulmonary hemorrhage. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

References

• Fuhrman & Zimmerman - Textbook of Pediatric Critical Care 6th edition. Chapter 52: Pneumonitis and interstitial Disease. Parakininkas D. Pages 603-607
• Reference 1: Martínez-Martínez MU, Oostdam DAH, Abud-Mendoza C. Diffuse Alveolar Hemorrhage in Autoimmune Diseases. Curr Rheumatol Rep. 2017 May;19(5):27. doi: 10.1007/s11926-017-0651-y. PMID: 28397125.
• Reference 2: States LJ, Fields JM. Pulmonary hemorrhage in children. Semin Roentgenol. 1998 Apr;33(2):174-86. doi: 10.1016/s0037-198x(98)80021-7. PMID: 9583112.

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

I'm Pradip Kamat coming to you from Children’s Healthcare of Atlanta/Emory University School of Medicine

and I'm Rahul Damania from Cleveland Clinic Children’s Hospital. We are two Pediatric ICU physicians passionate about all things MED-ED in the PICU. PICU Doc on Call focuses on interesting PICU cases & management in the acute care pediatric setting so let’s get into our episode:

In today's episode, we discuss about a 12-year-old male with lethargy after ingestion.

Here's the case presented by Rahul:

A 12-year-old male is found unresponsive at home. He was previously well and has no relevant past medical history. The mother states that he was recently in an argument with his sister and thought he was going into his room to “have some space.” The mother noticed the patient was in his room for about 1 hour. After coming into the room she noticed him drooling, minimally responsive, and cold to the touch. The patient was noted to be moaning in pain pointing to his abdomen and breathing fast. Dark red vomitus was surrounding the patient. The mother called 911 as she was concerned about his neurological state. With 911 on the way, the mother noticed a set of empty vitamins next to the patient. She noted that these were the iron pills the patient’s sister was on for anemia. EMS arrives for acute stabilization, and the patient is brought to the ED. En route, serum glucose was normal. The patient presents to the ED with hypothermia, tachycardia, tachypnea, and hypertension. His GCS is 8, he has poor peripheral perfusion and a diffusely tender abdomen. He continues to have hematemesis and is intubated for airway protection along with declining neurological status. After resuscitation, he presents to the Pediatric ICU. Upon intubation, an arterial blood gas is drawn. His pH is 7.22/34/110/-6 — serum HCO3 is 16, and his AG is elevated.

To summarize key elements from this case, this patient has:

• Lethargy and unresponsiveness after acute ingestion.
• His hematemesis is most likely related to his acute ingestion.
• And finally, he has an anion gap metabolic acidosis, as evidenced by his low pH and low HCO3.
• All of these salient factors bring up the concern for acute iron ingestion! In today’s episode, we will not only go through acute management pearls for iron poisoning, but also go back to the fundamentals, and cover ACID BASE disorders.
• We will break this episode down into giving a broad overview of acid base, build a stepwise approach, and apply our knowledge with integrated cases.

We will use a physiologic approach to cover this topic!

• Pradip, can you give us a quick overview of some general principles when it comes to tackling this high-yield critical care topic?
• Absolutely, internal acid base homeostasis is paramount for maintaining life. Moreover, we know that accurate and timely interpretation of an acid–base disorder can be lifesaving.
• When we conceptualize acid base today, we will focus on pH, HCO3, and CO2.
• As we go into each disorder keep in mind to always correlate your interpretation of blood gasses to the clinical status of the patient.
• Going back to basic chemistry, can you comment on the relationship between CO2 and HCO3?
• Yes, now this is a throwback. However, we have to review the Henderson–Hasselbalch equation. The equation has constants & logs involved, however in general this equation shows that the pH is determined by the ratio of the serum bicarbonate (HCO3) concentration and the PCO2, not by the value of either one alone. In general, an acid–base disorder is called “respiratory” when it is caused by a primary abnormality in respiratory function (i.e., a change in the PaCO2) and “metabolic” when the primary change is attributed to a variation in the bicarbonate concentration.
• Now that we have some fundamentals down, let’s move into definitions. Can you define acidemia and alkalemia and comment on how the sampling sites may vary these definitions?
• Acidemia is defined as an arterial pH below 7.35.
• Alkalemia is defined as an arterial pH above 7.45.
• Thus, normal pH range for an arterial blood gas is 7.35 to 7.45.
• Bicarbonate (HCO3) concentration, 21 to 27 mEq/L; and for PCO2, 35 to 45 mmHg.
• What about the venous side?
• Normal values for peripheral venous blood gases differ from those of arterial blood due to the uptake and buffering of metabolically produced CO2 in the capillary circulation and the addition of organic acids produced by the tissue bed drained by the vein.
• The range for peripheral venous pH is approximately 0.03 to 0.04 pH units lower than in arterial blood, the HCO3 concentration is approximately 2 to 3 mEq/L higher, and the PCO2 is approximately 3 to 8 mmHg (0.4 to 1.1 kPa) higher.

These subtleties are important physiological considerations as you trend blood gasses. For example, if you have a venous blood gas of 7.32, on the arterial side, it may be correlated to 7.35. Similarly on the venous side if you have a CO2 of 48, on the arterial side, this value may be about 5 mmHg lower, so around 43.

Rahul, we mentioned that prior to chasing gasses, it is important to assess the patient’s clinical state. Can you comment on this a bit further?

Yes, so the key here is that various signs and symptoms often provide clues regarding the underlying acid–base disorder; these include the patient’s vital signs (which may indicate shock or sepsis), neurologic state, pulmonary status (respiratory rate and presence or absence of Kussmaul respiration), and gastrointestinal symptoms (vomiting and diarrhea). We saw some of these in our case. We should also take into account any medications that affect acid–base balance in our assessment of acute acid-base changes. Relevant medications include laxatives, diuretics, topiramate, etc. Also, watch for specific ingestions such as methanol for example which can cause blindness.

As we dive into the various disorders, can you frame an approach to acid base blood gas interpretation?

Here are 3 steps:

Establish the primary acid base abnormality — are we dealing with an acidemia or alkalemia.Establish what value correlates with the primary acid base disorder:

CO2 HCO3

For example, when you diagnose an acidemia, a metabolic acidosis is characterized by a low serum HCO3. Also, it is important to note for each 10 mmHg pCO2, pH falls by 0.08 units.

Assess for compensation:

• For example, in a metabolic alkalosis, your lungs will compensate by increasing your CO2 via hypoventilation.
• Please note that renal compensation may take 24-48 hours after your initial respiratory acidosis/alkalosis.

Yes, I think this point of compensation is important to note especially when assessing for mixed disorders. If we take for example an acute respiratory acidosis, the normal compensatory response to acute respiratory acidosis is an increase in the serum HCO3 concentration by approximately 1 mEq/L for every 10 mmHg elevation in the PCO2. When the respiratory acidosis persists for more than three to five days, the HCO3 increases by approximately 3.5 to 5 mEq/L for every 10 mmHg elevation in the PCO2.

Important to note, with the exception of chronic respiratory alkalosis and mild to moderate respiratory acidosis compensatory responses do not usually return the arterial pH to normal.

Yes, in fact, in contrast with older data, data from more recent studies indicate that the pH in chronic respiratory acidosis may be normal and, in individual cases, higher than generally recognized (pH >7.40).

Let’s revisit our index case to review the acid base disturbance. Do you mind refreshing our memory on his initial ABG?

• pH 7.22/34/110/-6 — serum HCO3 was 16 meQ/L.

Rahul, take us through the step-wise approach:

1. Acidemia as evidenced by a low pH of 7.22
2. What supports an acidemia is a low bicarbonate so we can say it is metabolic
3. And in the case of a metabolic acidosis it is important for us to assess the degree of compensation using winter’s formula.

What is Winter’s formula?

• PaCO2 = 1.5 × [HCO3−] + 8±2 mm Hg
• In this case, our expected CO2 given our Bicarb is 16 would be 30-34, and our patient’s was 34, so this is a true metabolic acidosis.

The patient had an anion gap metabolic acidosis, can you tell us a bit more about what is the anion gap?

• Disorders that produce metabolic acidosis by increasing organic acid generation like in the case of ingestion or cases with increased accumulation of phosphoric and sulfuric acid such as severe chronic kidney disease can usually result in an increased serum anion gap.
• The anion gap can conceptually be understood as Na + All unmeasured cations  =  Cl + HCO3 + All unmeasured anions. In general it the is positives minus negatives, and clinically we simplify this as. Na - (Cl + HCO3), normal is 8-12. If the anion gap is elevated, we recognize that this is some organic acid that is creating a gap between positives and negatives.

Now Rahul, let's say we have a patient with hypoalbuminemia, would this affect the anion gap?

• Yes, it definitely can in healthy individuals, the major unmeasured anion responsible for the existence of a serum anion gap is albumin.
• This circulating protein has a significant net negative charge in the physiologic pH range. As a result, the expected baseline value for the anion gap must be adjusted downward in patients with hypoalbuminemia.
• Thus, Corrected serum anion gap  =  (Serum anion gap measured) + (2.5  x  [4.5 - Observed serum albumin])
• It is also important to note: In addition to hypoalbuminemia, marked hyperkalemia may affect the interpretation of the anion gap.

With a metabolic acidosis, think about two things, calculate anion gap & the Winter’s formula for compensation.

Clinically, what would be a good differential to keep in mind for an elevated anion gap metabolic acidosis?

• Traditionally the Mnemonic was taught as mud piles, however, I wanted to add a little bit of a flare, and that is considering "CAT MUDPILES":
• Carbon monoxide and Cyanide
• Aminoglycosides
• Theophylline
• Methanol
• Uremia
• Diabetic ketoacidosis
• Paracetamol/Acetaminophen, Paraldhyde
• Iron, Isoniazid, Inborn errors of metabolism
• Lactic acidosis
• Ethanol (due to lactic acidosis), Ethylene glycol
• Salicylates

Lactic acidosis is frequently encountered in the pediatric intensive care setting. It is one of our most common causes of an elevated anion gap metabolic acidosis and in general indicates poor oxygen delivery, mitochondrial paralysis, or increased oxygen consumption. Please review our podcast entitled oxygen delivery to review this foundational PICU concept.

• As an advanced integration, can you comment on the delta anion gap/delta HCO3 ratio in patients with elevated anion gap metabolic acidosis?
• The most common causes of acute, high AG acidosis in the PICU are are lactic acidosis and ketoacidosis. The degree to which the AG rises in relation to the fall in bicarbonate (HCO3) varies with the cause of the metabolic acidosis. When the AG increases in magnitude as a result of metabolic acidosis, that increase should be compared with the magnitude of the fall in HCO3.
• This represents the delta AG/delta HCO3 ratio, where delta AG is the patient's value of the AG minus the normal AG, and delta HCO3 is the normal serum HCO3 (ie, 24 mEq/L) minus the patient's serum HCO3
• In our patient, he had a delta AG of 9 divided by a delta HCO3 of 8. The normal value is between 1 & 1.6.
• What if you have a low delta AG/delta bicarbonate ratio?
• A lower value (in which the delta AG is less than expected from the delta HCO3) can be seen in a number of settings:
• In ketoacidosis, D-lactic acidosis, or toluene intoxication, the accumulating organic acid anions can be excreted by the kidney as sodium and/or potassium salts. As a result, in these disorders, the delta AG/delta HCO3 ratio is often below 1, and the serum AG may be normal.
• A higher value of the ratio above 1.6, usually reflects a mixed acid-base disorder in which a high AG acidosis coexists with a process that elevates the serum HCO3.
• As we pivot back to our case, he had an elevated anion gap metabolic acidosis 2/2 to acute iron poisoning, after the A B C tenants, what are our next steps in management?
• Severe symptoms and an anion gap MA are indications for iron chelation using (IV) deferoxamine. You would definitely want to consult with a medical toxicologist and/or regional poison control center.
• At times in acute iron overdose, you may note radio-opaque pills visible on a plain radiograph of the abdomen. This may also be a sign of severe poisoning.

Important to note, because iron does not bind to activated charcoal, GI decontamination for acute iron poisoning consists of whole-bowel irrigation (WBI) and, rarely, orogastric lavage via upper endoscopy. The severity of disease can be guided based on plain abdominal radiographs. In most patients, the risk of gastric lavage following iron overdose outweighs the limited benefit.

• To wrap up our discussion on metabolic acidosis, what are some common causes of non-anion gap metabolic acidosis?
• In the big picture, NAGMA usually results from a loss of bicarbonate or an isolated reduction in renal acid excretion.
• The most common NAGMA we see in the PICU:
• Diarrhea or NG losses
• Proximal (type 2) RTA or even Type 1 & Type 4 RTA where there is impaired renal acid excretion.
• We also frequently encounter hyperchloremia and a NAGMA with resuscitation of 0.9% normal saline as it provides a chloride load; adult studies show that infusing more than 3-4L can cause acidosis.
• Frequently as a fellow when we see a metabolic acidosis, we reflexively think about administering bicarbonate. Can you shed some clinical pearls on this management decision?
• I think in a pinch it is appropriate to consider, especially if blood pH is <7.1 or, in some patients, <7.2 & clinically the patient is deteriorating.
• Although intravenous bicarbonate may be helpful if administered to children with severe acute metabolic acidosis, the therapeutic focus should be on slowing the rate of acid generation (ie correcting the cause of acidosis).
• In general, shooting for a goal of pH >7.2 and/or serum bicarbonate concentration >16 mEq/L should be considered. We frequently dose Bicarbonate as 1-4 meQ/kg keeping in mind that your typical vial has 50 meQ of bicarbonate.
• As mixed disorders are important to also recognize let's conclude this episode by revisiting some compensation formulas.
• To review:
• Acute respiratory acidosis (less than a day) the serum HCO3 concentration increases by approximately 1 mEq/L for every 10 mmHg elevation in the PCO2 from normal.
• Chronic respiratory acidosis (usually three to five days) serum HCO3 increases by about 4 mEq/L for every 10 mmHg elevation in PCO2 in patients with chronic respiratory acidosis.
• Acute respiratory alkalosis, the serum HCO3 concentration reduces by 2 mEq/L for every 10 mmHg decline in the PCO2 from normal. In chronic, HCO3 will fall by 4 mEq/L.
• What about for a metabolic alkalosis?
• The respiratory compensation to metabolic alkalosis should raise the PCO2 by approximately 0.7 mmHg for every 1 mEq/L elevation in the serum HCO3 concentration.
• A very-easy-to-use relationship: PCO2  =  HCO3 + 10. Studies have shown that high CO2 levels are probably generated by respiratory muscle weakness associated with marked hypokalemia and potassium depletion, which almost invariably develop in these patients. This is classically seen in a baby with It may also help to obtain urine electrolytes such as urinary cl in metabolic alkalosis. We will visit an approach to urinary chloride interpretation in future episodes!

We talked about a wide breadth of topics today! Let's summarize…

Key objective takeaways:

1. Trend blood gasses based on similar sampling sites, remember for a peripheral venous sample, the range for pH is approximately 0.03 to 0.04 pH units lower than in arterial blood.
2. Have a step-wise approach for acid base disorders — we covered 1. establish alkalemia vs acidemia; 2. which value CO2 or HCO3 supports your primary disorder; 3. assess compensation
3. In metabolic acidosis, you'll have a low pH and a low bicarb, make sure that you do an Anion gap calculation, as well as Winter's formula.

This concludes our episode on the approach to acid base disorders. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

• More information can be found
• Berend K, de Vries AP, Gans RO. Physiological approach to the assessment of acid-base disturbances. N Engl J Med. 2014 Oct 9;371(15):1434-45. doi: 10.1056/NEJMra1003327. Erratum in: N Engl J Med. 2014 Nov 13;371(20):1948. PMID: 25295502.
• Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.328.
• Malatesha G, Singh NK, Bharija A, et al. Comparison of arterial and venous pH, bicarbonate, PCO2 and PO2 in initial emergency department assessment. Emerg Med J 2007; 24:569.

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. My name is Pradip Kamat

My name is Rahul Damania, a current 3rd-year pediatric critical care fellow and we are coming to you from Children’s Healthcare of Atlanta Emory University School of Medicine

Today's episode is dedicated to the transition between NICU & PICU. We will focus on the ventilation of the ex-premature infant who graduated from NICU care and transitioned to the PICU.

I will turn it over to Rahul to start with our patient case.

• Case: A 4-month-old ex-27 week baby boy is transferred to our PICU after an echo at an outside hospital showed elevated pulmonary pressures. The infant was born via a stat C-section due to maternal complications during pregnancy. His birth weight was 560 g. The patient was intubated shortly after delivery and had a protracted course in the NICU which included a sepsis rule out, increased ventilator settings, and a few weeks on inhaled nitric oxide (iNO).

1. The intubation course was complicated pulmonary hemorrhage on day 1 after intubation. After such an extensive NICU course, thankfully, the infant survived & was sent home on 1/2 LPM NC, diuretics, albuterol, inhaled corticosteroids, Synthroid, multivitamin with iron as well as Vitamin D. The patient was able to tolerate breast milk via NG tube and had a home apnea monitor with pulse oximetry.

• After about a week’s stay at home, the mother noted that the patient’s SPO2 was in the low 80s. The mother took the patient to the local hospital, where the patient was started on HFNC which improved his saturations. An echo done at the OSH showed elevated RV pressures (higher than the prior echo). The patient was subsequently transferred to our hospital for further management. At our hospital, the patient presented hypoxemic, tachycardic, and tachypneic. On physical exam: Baby appeared well developed, had a systolic murmur heard throughout the precordium, and there was increased WOB with significant intercostal retraction. There was no hepatosplenomegaly.
• Due to worsening respiratory distress, and increasing FIO2 requirement despite maximum RAM cannula, the patient was intubated and placed on conventional MV. A blood gas prior to intubation revealed a pH of 7.1/PCO2 of 100. An arterial line and a central venous line were also placed for better access and monitoring. Initial vent settings post intubation PRVC ventilation: TV 32cc, (25/10), 0.7 time, rate 0 (patient sedated/paralyzed).

To summarize, What are some of the features in H&P that are concerning for you in this case:

• Ex-27 week prematurity with a birth weight of 560 gms
• Prolonged MV in the NICU
• Home O2 requirement
• Abnormal echo showing high pulmonary pressures
• hypercarbia despite the use of RAM cannula

As mentioned, our patient was intubated, can you tell us pertinent diagnostics which were obtained?

• CXR revealed: Hazy airspace opacification in the right upper lung concerning developing pneumonia. Streaky airspace opacity in the left lung base medially may represent atelectasis.

I do want to highlight that the intubation of an ex-premie especially with elevated RV pressures is a high-risk scenario, it is best managed by a provider with experience, in a very controlled setting with optimal team dynamics. Adequate preparation to optimize the patient prior to the intubation as well as the knowledge to manage the post intubation cardiopulmonary interactions are essential. I would highly advise you to re-visit our previous podcast on intubation of the high-risk PICU patient by Dr. Heather Viamonte. Like many Peds ICU conditions, the management of the EX-NICU graduate in the PICU is a multidisciplinary team sport.

Our patient likely has the diagnosis of Bronchopulmonary Dysplasia or BPD, Pradip, can you comment on the evolving definition of this diagnosis?

• Let me first define BPD — Clinically, BPD is defined by a requirement of oxygen supplementation either at 28 days postnatal age or 36 weeks postmenstrual age. The literature stratifies the difference between old vs. new BPD definitions. In the old BPD, seen before the 1980s and in usually more mature infants - the pathogenesis is related to damage caused to the lungs from mechanical ventilation and/or oxygen resulting in inflammation/fibrosis. It can occur in premature as well as term infants. We see less of the old BPD due to the use of surfactant and HFOV use. In old BPD, we have e/o hyperinflation and diffuse parenchymal infiltrate -lung histology dilated distal airspace, fibrosis throughout the interstitium, and significant pulmonary arterial fibroproliferative disease

What about the new BPD?

New BPD: Refers to abnormal or arrest in lung development (fewer and larger alveoli) and decreased microvascular development in extremely low birth weight infants. In new BPD, we see more evidence of dilated distal lung, less evidence of fibrosis, more typically have an arrest of distal lung development, and still have vascular beds are abnormal. The key here is impaired lung surface area, decreased alveoli, and decreased vascular growth.

It is important to note that In severely affected infants, fibrosis, bronchial smooth muscle hypertrophy, and interstitial edema (“old” BPD) may be superimposed on the characteristic reduced numbers of alveoli and capillaries

Let's transition and speak about the pathogenesis of BPD, Rahul, what are the key risk factors?

• The important concept here is to understand the maternal fetal interface that can lead to premature birth. Determinants of disease include-Prenatal factors such as chorio-amniotic, fetal infection, IUGR, preeclampsia, maternal smoking/drug use with interplay from epigenetic/genetic factors, hyperoxia, inflammation, infection, ventilator induced lung injury can cause disruption of growth factor signaling pathways leading to changes in vascular growth, alveolar growth, and lung function.
• There is a 43% incidence (unchanged in the last 50 years) of BPD born < 29 weeks of age. The earlier one is born, the more severe is the BPD. At autopsy, one can see Regions of Hyperinflation, areas of atelectatic/edema and have pseudo-fissures between them, and dilated distal airways with little septae (”alveolar simplification).

Pradip, as it seems the histological architecture of the lung is altered, can you comment on the persistent respiratory disease seen in BPD?

Patients with BPD can have persistent respiratory disease, which can be seen as prolonged respiratory support/NICU hospitalization, chronic respiratory distress, recurrent exacerbations, re-hospitalizations, exercise intolerance, wheezing, and increased susceptibility to chronic lung disease in adulthood. These patients may require long-term ventilatory support via an ETT or tracheostomy.

To highlight epidemiology, did you know that 58% of preterm infants are readmitted to the hospital within the first year of life. 20% of these were admitted to the PICU and 12% ended up on MV.

Pradip, we mentioned the use of mechanical ventilation in BPD. Let’s pivot today’s episode and focus on management, understanding how to invasively ventilate a patient with BPD. How can we use our understanding of ARDS (say in an adolescent) to understand the ventilation strategies in BPD?

If we look at the lungs of a teenager with ARDS and hypoxemia, we may see diffuse parenchymal infiltrates. In these patients, the CT is will show a heterogeneous disease. There is a portion of the lung which may be susceptible to atelectasis, gravity dependent, and is edematous. It is this baby lung that we want to ventilate and recruit without overstretching. It’s balance. This is why we use the ARDSnet protocol which involves low tidal volumes, typically 6-8 mL/kg. We use prone positioning and increased PEEP to help recruit the lungs.

Great, let's contrast this with BPD, what are the radiographic and physiologic considerations in our patient who is now intubated in the PICU?

In BPD, the CT may show hyperinflation, diffuse infiltrates, peri-bronchial lesions, ground glass lesions, cystic lesions, etc. This is a stark contrast with ARDS. They can have large central airway diseases like tracheobronchomalacia, or subglottic or bronchial stenosis, and even granulomas. Patients with severe BPD can have small airway structural remodeling such as mucus gland hyperplasia and clinically we will see more secretions that are not cleared well due to ciliary dysfunction. These airways have an epithelial injury, edema, smooth muscle proliferation, broncho-constriction, and hyper-reactivity. The patients with BPD also have decreased alveolarization, decreased vascular growth (i.e. fewer vessels), abnormal vascular remodeling, tone, and reactivity as well as impaired lymphatic function. As these infants age, they can have sleep-disordered breathing, diaphragm dysfunction, and chest-wall instability. In summary, BPD affects not only the lung parenchyma, but the whole respiratory unit — pulmonary vessels, lymphatics, chest wall, and diaphragm!

Yes, it seems the take home is that the patient with severe BPD who is intubated in the PICU has vastly different physiologic and radiographic lesions compared to the run-of-the-mill teenager with acute ARDS. Hence a different ventilation and oxygenation strategy is required for the intubated BPD patient in the PICU. BPD subtypes include those with parenchymal lung disease, those with vascular disease (pulmonary arterial hypertension-evaluated at least initially with an echo), and those with airways disease (tracheo-bronchomalacia-evaluated by bronchoscopy). Additionally, a single patient may have more than one BPD subtype for example 28% can have all the above 3 subtypes. (Wu K et al. AJRCC Med 2020).

Before we dive deep into management how do you evaluate the underlying lung disease in patients with severe BPD?

We typically get CXR, blood gas, +/-Chest CT scan (may not require acutely), target SPO2 and PCO2, evaluate for chronic aspiration (ph probe, barium swallow, swallow study, etc.), sleep study, flexible bronchoscopy to evaluate structural airway disease as well as EKG, echocardiography, cardiac catheterization, etc may be required.

In terms of labs, lactates, BNP, and NT-pro BNP may be required on a case-by-case basis. Additionally, an Interstitial lung disease panel may also be required on a case-by-case basis. The management of the patient with severe BPD in the PICU is really a team sport, which involves the intensivist, the cardiologist, the pulmonologist, gastroenterologists, and support staff such as the speech therapist and the rehabilitation team. It also involves open discussions with family as these patients are hospitalized long term not infrequently. Family conferences at periodic intervals in collaboration with social workers can help optimize decision making, set goals of care, and allow for facilitation amongst teams.

Absolutely, it is a team sport!

Now Pradip, you mentioned the radiographic and lab evaluation of these patients who have chronic lung disease. As we think about continuous monitoring in the PICU, do you have some management pearls?

It is important to prevent hyperoxia by targeting an SPO2 of 92-94%. We also should avoid accepting an SPO2 of 90% as that can cause pulmonary hyper-vascular reactivity and these children can have marked vasospasm. We allow for permissive hypercapnia but avoid marked spikes or swings in PCO2 as long as pH is buffered. If PCO2 is chronically elevated its effect on PHTN is unclear. Elevated PCO2 may be a biomarker for severe parenchymal lung disease.

Rahul, we mentioned in the pathogenesis the abnormal vascular development in the pulmonary circuit, can you comment on the cardiopulmonary interactions seen in a patient with BPD?

In patients with severe BPD, we have High pulmonary artery pressures due to lung disease. Remember these children will have hyperinflation in some areas, atelectasis, and fluctuations in O2 and CO2. This can create chronic heart disease as well. Particularly RV dysfunction. Patients downstream can have issues with LV contractility as we have at times an exaggerated systolic interdependence which can affect LV contractility. The LV diastolic dysfunction may be due to persistent pulmonary edema. As these children are premature, it is also important to assess for abnormalities in cardiac development. These children will frequently have shunts. ASD, VSD, PDAs for example. The L to R shunting may create over-circulation, and in times of crises, these shunts may reverse leading to hypoxemia. Fortunately, when children have these shunts, they serve as “pop-offs” during times of increased pulmonary pressure. As we mentioned cath as one of our diagnostics it is important to assess for pulmonary vein stenosis as this fixed anatomic defect can further contribute to high pulmonary artery pressures.

In a summary, remember that the RV is relatively afterload sensitive and the LV is more sensitive to changes in preload!

As we set titrate the ventilator in our patient with BPD, Pradip, what strategies are you going to use for effective oxygenation and ventilation?

The biggest point before we go into the specific ventilator strategies is the heterogeneity of lung disease. This is not a two-compartment model as seen in ARDS. There is marked variability of regional time constants, and as mentioned, airway secretions, and pulmonary hypertension in many cases. Some areas of the lung may have normal compliance and resistance, whereas others may have poor compliance and high resistance. In this heterogeneous disease, there are also significant areas of high compliance and low resistance. So if we ventilate these patients with BPD with low tidal volumes, rapid rates, and low iTimes (similar to ARDS), we run the risk of having worse distribution of gas, increased dead space ventilation, hypercarbia, the need for higher FiO2 and radiographically progressive atelectasis.

As such, it is important for users to manage the patient with severe, chronic BPD with high TV. This allows for more gas to fill the lungs. Couple this high tidal volume, usually 8-10 mL/kg with higher iTimes and low rates to decrease the risk of atelectasis.

Ok, to summarize here, BPD patients, in general, have higher iTimes, higher tidal volumes, and low rates. This is to especially account for the areas of the lungs with higher time constants.

Rahul, real quick what is the definition of a time constant?

• The time constant is the time required for inflation of alveoli up to 63% of the final volume, or deflation by 63%. It is the product of resistance and compliance. For a normal set of lungs as a whole, the normal time constant is 0.1-0.2 seconds. In BPD, these children have varied, heterogenous time constants.

Rahul what about PEEP use in the intubated BPD patient?

• These patients in general require higher PEEP. It opens the airways and along with larger lung volumes has a tethering effect. This stretching effect with high peep may favor airflow and improves gas exchange. Like you frequently preach on rounds Pradip, PEEP is your friend! High PEEP with high rates can lead to air trapping and dynamic hyperinflation, so continue to reassess your patient, serial gas, x-rays, and ventilator scalars to determine the optimal rate to set on the ventilator in addition to the PEEP.

Let's take a holistic picture now, Pradip, beyond the ventilator, what do we have to consider?

• Don't rush towards extubation, but work to reduce distress, retractions, and “dyspnea”; at times growth with optimal nutrition is very beneficial. We need to optimize therapies such as OT and PT. but also consider the desaturations/increased PVR which may ensue during this hands-on care. We should focus on weaning sedation and NMB as tolerated.
• These children are in the PICU at times for long periods, so optimize day night cycles, sleep hygiene, lab schedules, and most importantly bonding with family & caregivers. Don’t forget to catch up on immunizations and ROP care. Remember Rahul, we are pediatricians first!!

I love these points, it is really a team effort. As we conclude this episode, in your opinion what does successful care of the BPD patient in the PICU look like?

• Successful treatment with BPD is synonymous with good supportive care — we want to do no harm. In this setting, we want ”minimal impact respiratory support”. Prevention of harm, prevention of infection, prevention of right heart failure, excellent nutrition for growth and repair as well as developmental assistance. You will frequently be coordinating care with your NICU or PICU...

Welcome to PICU Doc On Call, a podcast dedicated to current and aspiring intensivists. I am Pradip Kamat.

I am Rahul Damania, a current 3rd year pediatric critical care fellow.

I am Kate Phelps- a second year pediatric critical care medicine. We come to you from Children's Healthcare of Atlanta Emory University School of Medicine.

We are delighted to be joined by guest expert Dr Stephanie Jernigan Assistant Professor of Pediatric-Pediatric nephrology, Medical Director of the Pediatric Dialysis Program at Children’s Healthcare of Atlanta. She is the Chief of Medicine and Campus Medical Director at Children’s Healthcare of Atlanta, Egleston Campus. Her research interests include chronic kidney disease, and dialysis. She is on twitter @stephaniejern13

I will turn it over to Rahul to start with our patient case...

• A 3 year old previously healthy male presents with periorbital edema. Patient was initially seen by a pediatrician who prescribed anti-histamines for allergy. After no improvement in the eye swelling after a two week anti-histamine course, the patient was given a short course of steroids, which also did not improve his periorbital edema. The patient progressed to having abdominal distention and was prescribed miralax for constipation. Grandparents subsequently noticed worsening edema in his face, eyes, and feet. The patient subsequently had low urine output, low appetite and lack of energy patient was subsequently brought to an ED and labs were obtained. Grandparents denied any illness prior to presentation, fever, congestion, sore throat, cough, nausea, vomiting, gross hematuria, or diarrhea. In ED patient was noted to be hypertensive (Average systolic 135-highest 159mm HG), tachycardic (HR 130s-140s), breathing ~20-30 times per minute on RA with SpO2 92%. Admission weight was recorded at 16.5Kg. Physical exam showed periorbital edema, edema of ankles, there was mild abdominal distention (no tenderness and no hepatosplenomegaly), heart and lung exams were normal. There were no rashes on extremities.

Labs at the time of transfer to the PICU: WBC 10 (62% neutrophils, 26% lymphocytes) Hgb 7.2, Hct 21, Platelets 276. BMP: Na 142/K 8.4/Cl 102/HCO3 19/BUN 173/creatinine 5.8. Serum phosphorus was 10.5, Total Ca 6.4 (ionized Ca= 3.4), Mag 2.0, albumin 2.6, AST/ALT were normal. An urine analysis showed: 1015, ph 7.5, urine protein 300 and rest negative. Chest radiograph revealed small bilateral pleural effusions. After initial stabilization of his hyperkalemia-patient was admitted to the PICU. PTH intact 295 (range 8.5-22pg/mL). Respiratory viral panel including for SARS-COV-2 was negative. C3 and C4 were normal. A nephrotic syndrome/FSGS genetic panel was sent. A renal US showed: bilateral echogenic kidneys and ascites (small volume).

Pradip: Dr Phelps what are the salient features of the above case presented?

Kate Phelps: This patient has a subacute illness characterized by edema, anemia, and proteinuria. His labs show that he has severe acute kidney injury with significantly elevated BUN and Creatinine, hyperkalemia, hyperphosphatemia, and hypocalemia.

Rahul: Dr Jernigan welcome to PICU Doc on Call Podcast.

Thanks Kate, Rahul and Pradip for inviting me to your podcast. This is a such a great way to provide education and it is my pleasure to come today to speak about one of my favorite topics, pediatric dialysis. I have no financial disclosures or conflicts of interest and am ready to get started.

Rahul: Dr Jernigan as you get that call from the ED and then subsequently from the PCCM docs, as a nephrologists whats going on in your mind ?

When I get the call from the outside hospital my first job is to make sure the patient is safe and stable for transfer to a tertiary care center. This includes concern about airway, breathing and level of alertness. From a renal standpoint, I am worried about elevated blood pressure, electrolyte abnormalities, in this case primarily the hyperkalemia, and fluid overload, especially given the low oxygen saturation. It is important that children are transported to an appropriate center early, but still safely, to allow for diagnostic work up and intervention. This is particularly true in the case of renal replacement therapy which most community hospitals are reticent or unable to offer to our pediatric patients.

Our episode today will be divided into a few broad categories: INDICATIONS/PRINCIPLES of KIDNEY REPLACEMENT, TECHNICAL ASPECTS of RRT, Anticoagulation, and a comparison of various types of RRT and their complications.

Let’s start with INDICATIONS/PRINCIPLES of KIDNEY REPLACEMENT

Kate Phelps: What are in general indications for renal replacement in pediatric patients?

Indications for renal replacement therapy are similar for acute vs chronic dialysis however differ in their urgency. As we know, our kidneys are important for waste product elimination, a primary measurement of this is blood urea nitrogen, acid base and electrolyte balance and of course maintaining fluid balance. When these functions fail acutely so as to be dangerous to a patient or when they are chronically inadequate despite medical management, then renal replacement is indicated. Acute indications tend to be significant uremia which can have consequences on multiple systems (CNS, heart, coagulation), symptomatic fluid overload (affecting breathing and cardiac function), and/or hyperkalemia and intractable acidosis not responsive to medical intervention. Medical management includes for fluid overload the use of diuretics and the use of bicarb in order to correct acidosis and shift potassium intracellularly. Additional therapy for hyperkalemia – membrane stabilization with calcium, further increase of uptake of potassium by cells with glucose, insulin and Beta agonists and elimination of potassium in the gut with ion exchange resin (kayexlate). Not related to the kidney directly, dialysis may also be needed in toxic overdose (salicylates and acetaminophen, lithium, metformin to name a few) or inborn errors of metabolism resulting in hyperammonemia.

This has led to the mnemonic AEIOU – acidosis, electrolytes, ingestions, overload and uremia.

Uremia with a BUN of greater than 100 and symptomatic or greater than 150 even without current symptoms are concerning and in most cases indication for dialysis.

Less acute indication but no less important is need for dialysis when treatment and caloric nutrition are impeded by fluid issues and dialysis allows for these to be maximized without regard the secondary consequences of fluid imbalance.

Of note, while creatinine gives us a stable measurement of glomerular filtration rate, it’s value is not in and of itself an indicator for renal replacement therapy.

🎯 Just to summarize, acidosis – metabolic acidosis with a pH <7.1; electrolyte refractory hyperkalemia with a serum potassium >6.5 mEq/L or rapidly rising potassium levels; Intoxications

 – use the mnemonic SLIME to remember the drugs and toxins that can be removed with dialysis: salicylates, lithium, isopropyl alcohol, methanol, ethylene glycol; Overload

 – volume overload refractory to diuresis; Uremia

 – elevated BUN with signs or symptoms of uremia, including pericarditis, neuropathy, uremic bleeding, or an otherwise unexplained decline in mental status

Rahul: Dr Jernigan what physical principles are used in dialysis and what are the properties of the substances we can dialyze?

Let’s start with the principles of dialysis. Important here is understanding the laws governing movement of molecules between solutions and across a semipermeable membrane.

First is diffusion which is movement of molecules from a solution of higher concentration to lower concentration. This is much like “tea” where tea in the bag diffuses out into the water based on a concentration gradient. In diffusion, equilibrium will eventually occur and all things equal diffusion will slow and then stop. Smaller molecules will diffuse faster than larger molecules so this modality does better with smaller molecules.

Next is convection. Convection is movement across the membrane due to a pressure gradient, sometimes called solute drag. This can be compared to the making of coffee where water passed through the coffee grounds “pulling” or “dragging” the coffee (flavor and caffeine thank goodness) with it. This can be a pressure gradient (CVVH) or an osmotic gradient (PD)Convective therapies are better for larger molecular weight substances but removes small molecules as well.

Hemofiltration is movement of fluid across the membrane due to a gradient.

I believe we will talk more specifically about the different types of dialysis later however in brief, Hemodialysis utilizes primarily diffusion with the blood flow rate and the dialyzer being the factors that increases or decreases clearance.

PD uses both diffusion and convection equally but is not the most common modality seen in the ICU setting.

CVVH (continuous veno-venous hemofiltration) in its classic form uses primarily convection but has different modes which also allows for convection , diffusion and a combination of both.

So for best clearance molecules are smaller <10000 Daltons have high water solubility and small volume of distribution and low protein binding (most are greater than 10K Dalton, albumin is 66K Dalton)

To summarize, dialysis systems operate either via diffusion (i.e movement of molecules across a semipermeable membrane using a concentration gradient OR via convection where solutes move across a semipermeable membrane using a pressure gradient. In some modalities ultrafiltration occurs due to an osmotic pressure gradient. Lets transition to the next portion of our podcast which will cover vascular access & anticoagulation

VASCULAR ACCESS

Rahul: Dr Jernigan before we go into each modality, should we discuss the access required for RRT in the PICU?

Before we can begin dialysis we need access to the vasculature (HD and CRRT) and the peritoneal cavity (PD). Vascular access can be placed by you, our ICU colleagues, as well as interventional radiologists and surgeons. In general, we need a large gage vascular catheter. The smallest catheter utilized is 8 gage up to 14 gage. It is best placed in the internal jugular. The subclavian (the location of old) has been changed as complications during placement and vessel stenosis are problematic. This is especially true if future need of arteriovenous fistulas. If there is urgency of placement and especially in larger individuals (greater than 28 BMI) then femoral access may be needed but this has a higher infection risk and we worry about future vascular access for renal transplantation.

While old terminology included vas cath (temporary) and permcath (longer term), we have a system move to terminology that better describes the type of catheter placed. This includes single vs double lumen, low flow vs high flow, tunneled and cuffed (permanent) vs non tunneled. For dialysis we require double lumen and high flow. For long term, the catheter is tunneled and cuffed to allow for lesser infection and movement risk.

Peritoneal catheters are placed by surgeons. These are silicone or polyurethane and in best practice are double cuffed. The first cuff is placed under the skin and then the catheter is tunneled with the second cuff in the rectus muscle. The catheter then enters the peritoneal cavity where the coiled tip is placed in the pericolic gutter or pelvis. While they can be used urgently, the preference is to allow them to sit and heal for two weeks to avoid leakage and infection. The exception is in infants where this is the best option for many situations due to patient size.

ANTICOAGULATION

Kate: Dr Jernigan can you shed some light on the type of anticoagulation required during RRT?

Any time blood is circulated outside the body, it is at risk for clotting which leads to blood loss. For this reason, anticoagulation is required.

This original anticoagulation for blood dialysis is heparin and this is still the mainstay in hemodialysis. This is given as a bolus and thin continuous infusion until some point before discontinuation of dialysis as this is systemic anticoagulation (turned off sooner for fistula’s due to bleeding) Monitoring is through ACT’s however standard dosing is fairly well established and act’s used less often and not in the chronic unit. Starting bolus 20-50 units/kg and infusion of 10-30 units/kg/hr over remaining time.

Side effects are HIT (heparin induced thrombocytopenia) and bleeding risk due to systemic anticoagulation.

Citrate: This is used as regional anticoagulation meaning it only anticoagulates the circuit and not the patient. Citrate binds to calcium in the circuit and prevents activation of both coagulation cascades and platelet aggregation. The majority of the calcium–citrate complex is moves across the membrane by diffusion during dialysis and is lost in the ultrafiltrate. A systemic calcium infusion is necessary post filter to replace the calcium lost with citrate. Any calcium–citrate complex is not filtered and returns to the patient has a very short half life and is metabolized to bicarb by the liver, kidney and skeletal muscle. This citrate is titrated to blood flow to maintain low iCa in the circuit. The Calcium infusion is adjusted to keep iCa normal in the patient.

There are several advantages to citrate. First and foremost is the regional anticoagulation and less systemic bleeding, especially for those at high risk. It can be used in patients with HIT and in some patients, the additional bicarb from the citrate metabolism is helpful. The disadvantages are that in some patients the additional bicarb is not helpful and there can be other metabolic complications related to acid/base and calcium loss. In addition, with citrate there are the more complex protocols for the varying infusion rates and frequent calcium measurements. Citrate is relatively contraindicated in patient with hepatic failure and inborn errors of metabolism related to mitochondrial disorders.

Flolan: Epoprostenol, a naturally occurring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation and thrombus generation which is it’s mechanism to prevent clotting. For this reason it is avoided in patients with thrombocytopenia and should be used with caution in patients with hypotension. It has a short half-life and like other anticoagulants for CVVH is a continuous infusion of 2-8 ng/kg/min. Monitoring is simple and in addition to the above is circuit longevity.

🎯 Summary time — citrate binds calcium, be careful in patients with liver failure. With Flolan, watch for thrombocytopenia.

MEMBRANE

Pradip: Dr Jernigan what are the types of dialyzers used during RRT?

Hemodialysis dialyzers are primarily made of synthetic material. (polysulfone , poly mix) Synthetic membranes have less complement activation and systemic “allergic” reaction. They are made of multiple hollow semi permeable membrane fibers through which blood is flows with dialysate moving counter current outside the fibers. The effectiveness of the dialyzer is based on the thinness of the material and the number and size of the pores. There is a large surface area which in HD should approximate the patients BSA.

For prismaflex/CVVH we use two synthetic catheters the HF 20 and the HF1000 which are determined by patient size and clearance capability. HF 20 allows CRRT more safely on the small child weighing 8-20 kg.The volume of the dialyzer and tubing is important as in there is limit to the volume of blood that can be in the extracorporeal circuit. This is less than 10% of estimated blood volume and if more needs a blood prime. Keeping in mind that the extracorporeal tubing is also part of this calculation.

Although vascular access for dialysis in the PICU is easily attained by the intensivists, we have to be cautious about infants < 1 year of age. Due to fluid overload, platelet dysfunction (from uremia) etc., these are best done by the surgeon or interventional colleagues in a controlled setting. Pediatric Intensivists should be well versed with anti-coagulation choices during RRT.

RENAL REPLACEMENT MODALITIES

Dr. Phelps: Dr Jernigan what are modalities of renal replacement therapies typically used in children?

In children we can used peritoneal dialysis, hemodialysis, and continuous veno-venous hemofiltration (CVVH), CVVHD, or CVVHDF.

Rahul: Dr. Jernigan Lets start with peritoneal dialysis

After placement of the catheter, Peritoneal dialysis takes advantage of the large surface area of the peritoneal lining, a semi permeable bidirectional membrane to do dialysis by diffusion and convection.

PD is perfomed by instilling fluid, dianeal, into the peritoneal cavity which is then allowed to dwell for a prescribed amount of time (allowing solute movement via diffusion) and then drained. This is repeated for a prescribed number of cycles or time. Dianeal contains calcium, magnesium, sodium chloride and sodium lactate as a buffer. The variable in dianeal is dextrose which creates the osmolarity to allow for fluid removal and secondary solute drag (convection). The dextrose concentrations include 1.5%, 2.5% and 4.25% with higher dextrose pulling more fluid. As the peritoneal membrane is bidirectional, equilibration will occur so the fine art is to find the right dwell time to remove waste and fluid and drain before equilibration happens. Volumes range from 10-40 ml/kg and dialysis improves with increased volume and thus more membrane exposure to dianeal and by increasing time on dialysis.

In general PD is well tolerated and is the best dialysis for young babies with catheters being able to be placed in children weighing as little as 1.8 to 2kg without needing blood exposure as in hemodialysis. While inpatient, PD can be done with a manual exchange set for very small volumes and once appropriate volumes obtained transitioned to an automated cycler.

In addition to its advantage in the smallest patients, other advantages of PD include less need for specialized equipment and highly trained extracorporeal personnel. It does not require vascular access or anticoagulation. Electrolyte shifts are gentle and slow. In the outpatient world, PD is done at home and daily so has advantages to quality of life. Concerns include that waste and fluid removal are variable and may not be acute or aggressive enough for some ill children (fluid overload or hyperkalemia) and PD is not great acute therapy due to concerns for leakage with a fresh catheter. Instilling fluid into the abdomen may impinge on respiratory excursion could be an issue for some patients and as this modality does rely on adequate blood pressure to perfuse the peritoneum, it hypotension present, if may be less effective. Recent or impending abdominal surgery or gastroschisis /omphalocele are contraindications however VP shunts, ostomies and Eagle Barret...

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

I'm Pradip Kamat

I'm Rahul Damania, a third-year PICU fellow.

I’m Kate Phelps, a second-year PICU fellow and we are all coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine, joining Pradip and Rahul today. Welcome to our episode, where will be discussing gastrointestinal bleeding.

Kate: Let’s start with a case:

A 4-year-old, previously healthy male presents to the emergency room after a large, bloody stool at home. He notably had an episode of dark emesis and an episode of blood-tinged emesis on the day prior. In triage, he is altered and unable to answer questions coherently. Initial vital signs are temperature 36.1 C, RR 24, HR 146, BP 110/54. Point-of-care labs show hemoglobin to be 5.1 with hematocrit 15. His venous blood gas is reassuring against respiratory disease, and he is in no respiratory distress. Further labs are sent and a massive transfusion protocol is initiated before transfer to the PICU. Before arrival in the PICU, he receives two aliquots of RBCs, 1 aliquot of FFP, and 1 aliquot of platelets. Additional labs are sent from the PICU, post-transfusion. His post-transfusion hemoglobin is 8.8. Other labs are notable for normal MCV, elevated total bilirubin to 4.1 (with direct component 3.4), and elevated AST and ALT to 309 and 495 respectively.

Rahul: To summarize key elements from this case, this patient has:

• An undifferentiated gastrointestinal bleed with both hematemesis and hematochezia.
• He has symptomatic anemia, as evidenced by tachycardia
• Altered mental status.
• He is initially stabilized via transfusion of several blood products and liver function labs are shown to be very abnormal — which we will get more into later!

PK: Let’s get into important parts of the history and physical. Kate, can you tell me what some key history items in this patient are — and what are some areas to make sure to touch on when a patient has a GI bleed?

Kate: Yeah! I’d love to.

First - in our patient, some important elements are his rather acute onset. His parents mention he has had one day of bleeding symptoms - first with emesis yesterday, with components of old, partially digested blood, as well as some fresh blood. Second, he has a frankly bloody stool at home. Given his clinical instability, history taking was probably limited at first, so it’s important to ask follow-up questions and really dig into the case after stabilization!

I like to put my questions about gastrointestinal bleeding into buckets based on the questions I need to answer. I need to answer: is this active bleeding or old blood? Is this slow, insidious bleeding or fast, life-threatening bleeding? Is this an upper GI bleed or a lower GI bleed? Bright red blood in emesis tells us that bleeding is active, whereas coffee-ground or dark emesis tells us that, while recent, the blood has been partially digested in the stomach and may not be ongoing. Similarly, melena (dark, tarry stool), tells us blood has come through the colon. While coffee-ground emesis and melena don’t rule out an active bleed, they do tell us the bleeding may be slower, as large volume, active bleedy is irritating to the stomach and gastrointestinal tracks and moves through the system quickly.

The next question I want to answer is: what is the cause of this bleed? Easy bruising, petechiae and mucosal bleeding may point to a coagulation disorder. Abdominal cramping, frequent stooling, and weight loss may point to inflammatory bowel disease. Past medical history, family history, and a thorough review of systems are key here.

Rahul: Yeah, that’s great! Let’s talk about your question of upper GI vs lower GI bleed.

First, a definition: an upper GI bleed is bleeding that occurs above the ligament of Treitz — which is ligamentous tissue that supports the end of the duodenum and beginning of the jejunum at their junction. While not 100% specific, some symptoms that point to an upper GI bleed are: hematemesis, coffee-ground or dark emesis, and melena. Symptoms that lend themselves to the diagnosis of a lower GI bleed are hematochezia (bright red blood in the stool) and melena (which may represent a more bleed more proximal to Treitz). However, with a brisk, heavy upper GI bleed — say from the duodenum — patients can also have hematochezia.

OK to summarize, when we think of GI bleeding, first stratify your patient into slow vs. fast bleeding, identify whether it is upper or lower GI bleeding, and dive deeper into an underlying cause after your patient is stabilized.

Pradip: Relatively little data exists about the prevalence of GI bleeds in the PICU. In a study by Chaibou, et al., they reported that approx 10% of PICU children have upper GI bleeding with only 1/5 of those with UGIB having clinically relevant bleeding (characterized by significant hemoglobin drop, need for transfusion, hypotension, multi-organ failure, or death). Incidence of lower GI bleeding is even less well characterized in current available evidence.

Kate: Thanks, Pradip. Given our patient’s symptoms, I would be most concerned for an upper GI bleed, given the bloody emesis — but a significant one if it’s leading to hematochezia.

Rahul: Yeah, that’s exactly what I was thinking, KP. Pradip, in the literature we see they mention that NG saline lavage can be used diagnostically to help confirm if bleeding is occurring in the upper GI tract vs a pulmonary source. Further, NG lavage has been advocated as a therapeutic practices, however, this may be outdated now as we push for more timely endoscopy. In fact, studies show: ice water lavage is not recommended; this older practice does not slow bleeding and may induce iatrogenic hypothermia, particularly in infants and small children.

Kate: Ok, let’s back up for a second — let’s talk about red flag symptoms! ABCs should always come first for every patient who arrives anywhere in the hospital. In this patient, concerning symptoms in this scenario, are his tachycardia and his altered mental status. These symptoms tell us that anemia is symptomatic and likely more acute. Hypotension and tachycardia indicate that bleeding is significant enough to cause hypovolemia. Altered mental status indicates that the brain is hypoxic, in this case, due to inadequate hemoglobin. Other red flags symptoms in GI bleeding include: orthostatic changes, delayed capillary refill and other signs of poor perfusion, currant jelly stools (which may indicate bowel ischemia), and of course anything that points to a large volume of blood in emesis or stool (for example, “the whole toilet bowl was red”) — as these may precede hypotension. Rahul will fill us in later about how to treat patients with red flag symptoms!

Absolutely, the identification of hypovolemic shock is essential in GI bleeding. Notice subtle data trends and optimize O2 delivery. Please check out our prior episode entitled Oxygen Content & Delivery.

Pradip: To switch gears, tell me how you think about the differential in patients with bleeding?

Kate: Sure, the differential will be different for upper vs lower but will also be relevant to the age of the patient. The differential for clinically relevant GI bleeding in an infant includes hemorrhagic disease of the newborn (in those who did not receive Vit K at birth), necrotizing enterocolitis, and Hirschprung’s enterocolitis (which interestingly can occur after repair), and volvulus. For children >1 year, the differential includes esophageal varices, gastric or duodenal ulcers, volvulus, intussusception, Meckel’s diverticulum, Mallory Weiss tears, IgA vasculitis, hemolytic uremic syndrome, and several infectious etiologies. Adolescents and young adults have a similar differential but now we begin to think more about inflammatory bowel disease and NSAIDs. Of course, there is a lot of overlap between school-age children and adolescents. In the oncology population, we have to think about graft-versus-host disease and typhlitis.

Rahul: So really — the differential is broad. Let’s talk about initial and ongoing work up to narrow our differential.

Initial labs should include a complete blood count, a comprehensive metabolic panel with a fractionated bilirubin, coagulation studies, and — perhaps most importantly — a type & screen! Initial imaging might include a two-view abdominal X-ray to evaluate for obstruction or perforation. Ultrasound can help rule in intussusception. Later imaging might include CT with angiography or even MRI.

Remember when it comes to liver function tests: alkaline phosphatase and GGT give us info about the biliary ducts, AST and ALT tell us about hepatocellular function, and albumin and PT/INR give us info about hepatic synthetic function.

Pradip: Great — now let’s get into treatment.

Rahul: As Kate eluded to earlier, if any red flag symptoms are present, we need to think about resuscitation and stabilization. Initial stabilization for patients should include attention to the airway, breathing, and circulation. For serious upper GI bleeds, intubation should be considered for repeated bloody emesis, to control the airway and prevent aspiration. Hypotension can be initially managed with judicious fluid resuscitation to temporize but should be followed by blood products as soon as possible. Most hospital centers have a massive transfusion protocol, so consider this in hemorrhage states before you have signs of end-organ hypo-perfusion! Kate, can you touch on additional specific treatment for ongoing bleeding?

Kate: Yeah - we really have two avenues for intervention: medical and surgical. Medical treatment can be tailored to the etiology but can include an IV proton pump inhibitor (or PPI) as first like during workup, followed by an octreotide infusion. Rahul, can you tell us about octreotide before I continue?

Rahul:

• Octreotide is a Long-acting somatostatin-analog: that reduces splanchnic blood flow and inhibits gastric acid secretion.
• Dosing: an initial bonus of 1 mcg/kg followed by a maximum infusion of 10 mcg/kg/hr, which can be titrated down as bleeding improves and resolves.
• Side effect: hyperglycemia as we inhibit the effects of insulin.

Kate: Perfect- thanks! An additional medication sometimes used in GI bleeding is vasopressin, though octreotide has been shown to be as efficacious and does not carry the same daunting side effect profile. Most management strategies have shifted to using octreotide over vasopressin. If intermittent PPI dosing plus octreotide doesn’t control bleeding, a continuous infusion of a proton pump inhibitor can be considered though no data has shown this.

Let’s summarize the medical therapies, PPI, octreotide, and in some cases vasopressin.

Pradip: For surgical intervention, we’re first talking about upper endoscopy (esophagogastroduodenoscopy) or a colonoscopy — which can be both diagnostic and therapeutic. Endoscopy should ideally occur after hemodynamic stabilization but within 12 hours of admission for variceal bleeding and within 24 hours of admission for non-variceal bleeding in the case of upper gastrointestinal sources. Endoscopic interventions may include: adhesive cyanoacrylate applied to the bleeding lesion, band ligation applied to varix, injection sclerotherapy, and epinephrine injection, among other things. Interventional radiology may be able to perform arterial embolization.

Kate: I think this is the perfect point to follow up with our case, initial labs point toward normocytic anemia biliary duct obstruction without coagulopathy. During the hospital admission, bleeding stabilized after the initial massive transfusion. EGD showed acute clot formation near the ampulla of Vater in the duodenum. The eventual MRI showed a choledochal cyst with arterial erosion leading to the acute hemorrhage. An angiogram and percutaneous biliary drain placement were accomplished with IR.

OK Kate, do you mind summarizing our takeaways for today?

Kate: Key objective takeaways:

1. Clinical relevant GI bleeds are uncommon in the PICU, but the skills to stabilize are crucial in the setting of a life-threatening hemorrhage.
2. The differential for a GI bleed is broad but can be narrowed through careful and thorough history taking, physical examination, laboratory data, and imaging.
3. Endoscopy should occur in a timely fashion in the setting of clinically significant upper GI bleeding.

• For more reading, information can be found in:
• Pediatrics in Review, “Gastrointestinal Bleeds” by Baker, et. al in the October 2021 edition.
• Chapter 95 of the most recent edition of Fuhrman & Zimmerman’s Pediatric Critical Care, with sections on many of the differential diagnoses, included today.

This concludes our episode on GI hemorrhage. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is hosted by myself Dr. Pradip Kamat, and my dream cohosts Dr. Rahul Damania and Dr. Kate Phelps. Stay tuned for our next episode! Thank you!

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

I'm Pradip Kama and I'm Rahul Damania, a third-year PICU fellow. I’m Kate Phelps, a second-year PICU fellow and we are all coming to you from Children's Healthcare of Atlanta, Emory University School of Medicine, joining Pradip and Rahul today. Welcome to our episode, where will be discussing rhabdomyolysis and associated acute kidney injury in the ICU.

Rahul: Here's the case, a 7-year-old female presents to the ED with three days of fever, poor PO, and diffuse myalgia. In the ED, her vital signs are T 39.1C, HR 139, BP 82/44, RR 32. She is pale and diaphoretic, complaining weakly about how much her legs hurt. Her parents note that she has not been peeing very well since yesterday, and when she does pee it is “very concentrated, almost brown.” She’s also been spending all her time on the couch and has asked to be carried to the bathroom when she does need to go.

An IV is placed by the emergency room team, and she is given a fluid bolus, acetaminophen, and initial labs are drawn (CMP, CBC, RSV/Flu swab) before she is admitted to the PICU. In the PICU, her fever is better and her vitals have improved to T 37.7, HR 119, BP 115/70, and RR 25. Her respiratory swab has just resulted positive for Influenza A. Further labs are sent, including creatine kinase (CK), coagulation studies, and a urinalysis. Labs are notable for K 3.9, Bicarb 22, BUN 15, Cr 0.8, and CK 5768 IU/L. Her urinalysis is notable for 1 WBC, 2 RBC, +3 blood, negative nitrites, and leukocyte esterase.

Kate: To summarize key elements from this case, this patient has:

• Influenza A, as evidenced by her respiratory swab, as well as her clinical prodrome.
• She has diffuse myalgias, as well as fevers, diaphoresis, and hypotension.
• Labs are most notable for elevated creatinine and elevated creatine kinase, as well as an abnormal urinalysis.
• All of which brings up a concern for rhabdomyolysis and myoglobin-induced acute kidney injury.

Before we get into this episode — let's create a mental framework for this episode — we will dissect our case by highlighting key H&P components, visit a differential diagnosis, pivot to speaking about pathophysiology, and finally, speak about management!

• Rahul: Let's transition into some history and physical exam components of this case.
• The classic presentation of rhabdomyolysis is myalgias, muscle weakness, and tea-colored urine, all of which our patient has. Decreased urinary output can also accompany, a variety of reasons, but most notably if the patient has myoglobin-induced acute kidney injury. In our patient, poor PO is also probably contributing to her decrease in urine output. Red flag signs or symptoms will include anuria, hypotension, and altered mental status (which is rare but may indicate severe acidemia and deterioration)
• Pradip: As we think about our case, what other disease processes might be in our differential? As we dive in a bit more, we’ll come up with ways to distinguish between rhabdo and other things!
• Viral myositis - inflammation in the muscles in the setting of a viral illness, which can definitely happen with influenza and other common viruses
• Some other things which may cause reddish-brown urine, including hematuria, hemoglobinuria, porphyria, some specific foods or drugs (like rifampin, beets, food coloring — even ibuprofen)
• We also have to investigate a bit more to convince ourselves that our patient’s AKI is due to rhabdomyolysis, as it could be from dehydration, sepsis, NSAIDS, etc.

Kate: Let’s dive further into rhabdomyolysis!

Rhabdomyolysis affects over 25,000 adults and children every year. While toxins (including prescription drugs, alcohol, and illicit drugs) and trauma are two common causes of rhabdo in adults (and teens), infections, especially viruses, are the most common cause in young children. Influenza, EBV, and CMV are three most commonly reported.

What’s the pathophysiology of Rhabdomyolysis?

Rhabdomyolysis is the injury of skeletal muscle, which leads to cellular damage, apoptosis, and necrosis. As a result, skeletal muscle cells lyse and release their intracellular contents. Insult directly to the cell membrane and ATP-depletion are two mechanisms that can start the chain reaction leading to this cell death.

When the cell membrane itself is injured (as may happen in trauma or crush injury, metabolic conditions, or toxins), ionized calcium can freely enter the cell, leading to activation of proteases and phospholipases, which further injure the cell membrane, as well as mitochondria. As a result, the cell undergoes apoptosis and necrosis. When there is an ATP-depletion, pumps on the cell membrane important for maintaining sodium and calcium homeostasis between the intracellular and extracellular components become compromised. Intracellular calcium levels build, and the same process of cell and mitochondrial injury leads to apoptosis and necrosis.

To summarize, Rhabdomyolysis is an index example of cell adaptations, injury, and death. The key here is cell membrane damage which leads to downstream apoptosis.

Absolutely Rahul, the danger of this is that other intracellular contents are released into the extracellular space, including myoglobin, potassium, uric acid, intracellular enzymes, and many other things. Creatine kinase, or CK, released from cells is relatively indicative of rhabdo. Though no consensus criteria for rhabdo exist, most experts agree that serum CK level >1000 IU/L combined with the history and physical findings we will discuss is consistent with rhabdomyolysis.

This is especially important as there is are a multitude of pathologies that can cause a mild, transient increase in CK levels usually < 1000.

Pradip: One of the most common and most dangerous complications of rhabdomyolysis is acute kidney injury. While more common in adults, AKI occurs in ~5% of children with rhabdomyolysis. Let’s take a brief moment to discuss rhabdomyolysis-induced, or more specifically myoglobin-induced, acute kidney injury. While the mechanisms for myoglobin injury to the nephron aren’t entirely clear, most experts believe one of three things or, more likely, a combination of three things occur. Rahul, can you walk us through those?

Rahul: Sure, I’d love to!

• First, myoglobin is directly nephrotoxic, though notably only in an acidic environment!
• Second, it causes oxidation of ferrous oxide, leading to free radicals and reactive oxygen species, unregulated by usual intracellular processes.
• Third, myoglobin, through protein-binding, can precipitate in the tubule, leading to obstructive nephropathy.

Kate: Whew! That is a lot! Let’s take a break and review what we just learned:

Rhabdomyolysis is the injury of skeletal muscle leading to calcium influx into cells, which cascades into eventual apoptosis and necrosis. This leads to a massive release of intracellular components that upsets the overall homeostasis of the intra- and extracellular spaces. Myoglobin released from cells can directly injure the kidneys, leading to AKI. Potassium and hydrogen proton leakage, combined with AKI, can lead to life-threatening hyperkalemia and acidosis. CK is a serum measurement that can help confirm the diagnosis of rhabdomyolysis.

Rahul: Fun Fact Myoglobinuria usually only occurs in rhabdomyolysis (BUT not all rhabdomyolysis has myoglobinuria as it only spills out in urine above certain serum concentrations). Myoglobinuria can be inferred from a urine dipstick when there is moderate or large blood but few or no red blood cells. This is because the dipstick test for blood is non-specific for hemoglobin vs myoglobin! Myoglobin is also the reason the urine turns reddish-brown or “tea-colored.”

Pradip: Let’s change gears and talk about management. Kate, can you tell us about the management of rhabdomyolysis?

• Kate: With this patient, our first step should be resuscitation — always ABCs first! After initial fluid resuscitation and stabilization, we can begin to think about further workup and screening. Labs should include a comprehensive metabolic panel (CMP), urinalysis with dipstick, complete blood count, and creatine kinase. Depending on the severity of clinical illness, coagulation studies can be sent, as DIC is a rare complication of rhabdomyolysis, as well as sepsis, which is on our differential! In rhabdo, labs will show an elevated CK, possible hyperkalemia, acidosis, hyperphosphatemia, and hyperuricemia. If kidney injury is present, hyperkalemia is more likely, in addition to elevated creatinine.
• Once rhabdomyolysis is confirmed, treatment should focus on hydration, hydration, hydration! Additionally any complications of abnormal electrolytes, etc, should be monitored for and addressed. This includes telemetry monitoring or EKG in the setting of hyperkalemia.

Rahul: Remember, symptomatic hyperkalemia as evidenced by EKG changes, including wide QRS, absent P waves, or arrhythmias, including ventricular fibrillation, should be treated immediately. IV calcium administration will stabilize the cardiac membrane. Bicarbonate, insulin + glucose, and albuterol can quickly but only temporarily shift potassium into cells. Kayexalate and diuretics can remove potassium from the body.

• Pradip: Hydration is the most important treatment in rhabdomyolysis. There is a paucity of data, but most expert consensus suggests targeting a urine output of 3-4 ml/kg/hr while administering 2x maintenance fluids for children with rhabdo. Which fluid is the right fluid is still an area for more research, as studies have shown conflicting data about the benefits of NS vs LR vs bicarb-fluids. Normal saline without potassium can be used. Bicarbonate-containing fluids can be considered to buffer the urine on a case-by-case basis.
• Kate: And treatment of AKI should include avoidance of nephrotoxic medications and treatment of the underlying etiology. Renal replacement therapy should be considered for refractory fluid overload in the setting of oliguria or anuria, refractory acidosis (with pH<7.1), and refractory or life-threatening hyperkalemia. Remember those AEIOU reasons for RRT!
• With the resolution of the underlying cause, CK should peak in 3-5 days and then start to down-trend. Patients can be considered safe for discharge with the return of kidney function, normalization of electrolytes, and resolution of myoglobinuria.

We should note here that underlying metabolic myopathies can cause recurrent, mild rhabdomyolysis, though these children do not usually need critical care unless the cause for an exacerbation is sepsis or other potentially life-threatening illness!

• Kate: To wrap up, here are some take-away points:
• The key is hydration, hydration, hydration for the treatment and prevention of life-threatening electrolyte abnormalities and acute kidney injury in the setting of rhabdomyolysis
• If present, myoglobinuria indicates rhabdomyolysis.
• In children, viral illness is the most common cause of rhabdomyolysis, while toxins and trauma are more common in older teens and adults.
• Rahul: More information can be found
• “Rhabdomyolysis and acute kidney injury” from Bosch, et al, in the July 2009 issue of the New England Journal of Medicine and,
• “Pediatric rhabdomyolysis” in the June 2020 Pediatrics in Review
• References: (don't read these)
• Szugye HS. Pediatric Rhabdomyolysis. Pediatr Rev. 2020 Jun;41(6):265-275. doi: 10.1542/pir.2018-0300. PMID: 32482689.
• Nance JR, Mammen AL. Diagnostic evaluation of rhabdomyolysis. Muscle Nerve. 2015 un;51(6):793-810. doi: 10.1002/mus.24606. Epub 2015 Mar 14. PMID: 25678154; PMCID: PMC4437836.
• Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009 Jul 2;361(1):62-72. doi: 10.1056/NEJMra0801327. Erratum in: N Engl J Med. 2011 May 19;364(20):1982. PMID: 19571284.

Pradip: This concludes our episode on rhabdomyolysis. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania — with special guest Kate Phelps today. Stay tuned for our next episode! Thank you!

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

Welcome to our Episode about a 14- year- old female who presented with hypotension after a suicide attempt.

Here's the case:

A 14 yo F with PMH of depression and oppositional defiant disorder presents with dizziness. Her mother states she was in her normal state of health when on the day of admission she noticed the patient to be dizzy, slurring speech, and pale. The mother became very concerned about the dizziness as the patient was stumbling and a few hours prior to presentation, became increasingly sleepy. The patient does have a history of depression and is controlled on sertraline. Other medications in the home include Metformin, Amlodipine, and Clonidine. The patient denies ingesting any substance. She does have a prior attempt two years prior, after an argument with her mother; however, her mother was able to “stop” her prior to the attempt. She presents to the ER via EMS. Her vital signs are notable for HR 50 bpm with occasional PACs and non-conducted QRS complexes on telemetry; BP of 75/40. A physical exam is notable for AMS and GCS of 10. She is noted to have clear breath sounds, with a cardiac exam notable for slowed and delayed pulses. Initial laboratory work is notable for serum glucose 180 mg/dL and B HCG negative. Initial resuscitation is begun with IV fluids and atropine. Serum acetaminophen and ASA levels are sent and upon stabilization, the patient presents to the PICU for admission.

To summarize key elements from this case, this patient has:

• A history of depression with prior attempt
• An acute bout of altered mental status
• Bradycardia, hypotension, and hyperglycemia.
• All of which brings up a concern for an acute ingestion
• Let’s take a step back and talk about the approach to ingestions in the PICU.

1. What are key aspects to consider in the work-up of these patients?

• History and physical are key:
• Stratifying acute or chronic ingestions
• Baseline prescription medications a patient may be taking or have access to in the household
• Whether the ingestion involves a single drug or co-ingestants are all first steps in evaluating your patient.
• In an undifferentiated patient, management is paramount. Initial management is focused on pattern recognition and acute stabilization.
• A brief initial screening examination should be performed on all patients to identify immediate measures required to stabilize and prevent deterioration of the patient. Assess the airway, vital signs, mental status, pupil size, and skin temperature and moisture.

These components of your physical exam should help allude to a toxidrome, and these syndromes are frequently tested on board examinations. Any time a patient has hypotension and bradycardia other drugs that should be considered include beta blockers, digoxin, clonidine, as well as ingestion of barbiturates, opioids, and even benzodiazepines.

1. What are some diagnostic studies you will want to send immediately in a patient with suspected ingestion?
2. Immediate diagnostic studies to be performed include pulse oximetry, continuous cardiac monitoring, an electrocardiogram (ECG), and a capillary glucose measurement (in altered patients). Intravenous (IV) access should be obtained in all cases of serious ingestion.
3. You also want to send beta-hcg and acetaminophen and salicylate levels. an extended toxicology screen may be required on a case-by-case basis.

One study found detectable serum acetaminophen concentrations in 9.6 percent of all overdose patients; almost one-third of this subset denied ingestion of acetaminophen.

1. Now that you’ve focused on ABCs are there more detailed laboratory studies to send in patients with toxidromes?
2. Symptomatic patients and those with an unreliable or unknown history should, at a minimum, undergo urinalysis and measurement of serum electrolytes, blood urea nitrogen (BUN), creatinine, and glucose. Measurements of serum ketones, creatine kinase, liver function tests, lipase, ionized calcium, and magnesium should also be performed in most significantly ill patients.
3. Additional testing may be useful in specific circumstances, such as serum osmolality in suspected toxic alcohol ingestion. We will discuss these in a separate episode.
4. Patients who continue to be altered may also undergo head CT as head trauma is frequently associated with ingestions.
5. ECG, Echocardiography helps to distinguish refractory hypotension due to vasodilatation from pump failure. CXR may be needed to evaluate pulmonary edema and guide fluid management. Abdominal radiograph or US may be required in cases of suspected bowel ischemia/perforation. Ingestion of a large number of CCB tablets, especially sustained-release tablets, the pills may aggregate to form bezoars and the drug can be continuously absorbed for long periods.
6. To go back to our case, with history and initial diagnostics only, how are we able to stratify whether this patient took a CCB versus a beta-blocker?
7. This is a great question. This patient had an electrocardiogram, which showed changes associated with CCB poisoning including a PR interval prolongation and bradydysrhythmia. Importantly, our patient’s serum glucose was >150 mg/dL and thus, the presence of hyperglycemia in a non-diabetic patient may help to distinguish CCB from beta-blocker poisoning.

The mechanism of hyperglycemia in CCB involves the CCB causing inhibition of calcium-mediated insulin release; remember that the serum glucose elevation is rarely clinically significant, and is used for diagnostic purposes to stratify between bb and CCB overdose.

Per history, our patient had access to amlodipine which is the likely agent she ingested. Can you shed some light on how non-DHP CCB overdoses are different than DHP overdoses?

• Let’s review some basic science & pharmacology:
• Calcium channel blockers (CCBs) can be divided into two major categories based on their predominant physiologic effects: dihydropyridines, which preferentially block the L-type calcium channels in the vasculature; and non-dihydropyridines, such as verapamil and diltiazem which selectively block L-type calcium channels in the myocardium.
• L-type calcium channels are responsible for myocardial contractility and vascular smooth muscle contractility; they also affect conducting and pacemaker cells.
• In general DHP (which has the suffix dipine) are potent vasodilators that have little negative effect upon cardiac contractility or conduction at standard doses.
• In contrast, verapamil and diltiazem are relatively weak vasodilators but have a depressive effect on cardiac conduction and contractility.
• How does this framework help with our understanding of CCB ingestions?
• Overdose with dihydropyridine CCBs (amlodipine/nifedipine) causes hypotension coupled with reflex tachycardia, although severe toxicity may result in hypotension and bradycardia. This is what we saw in our patient — severe toxicity.
• Overdose with non-DHP CCB like verapamil or diltiazem also causes a dangerous combination of hypotension and bradycardia. As these are cardiac-specific, other findings may include signs of heart failure (eg, pulmonary crackles or jugular venous distension). In anecdotal articles, CCB-poisoned patients may maintain a surprisingly clear mental status in the setting of hypotension.

Let’s conclude our episode by focusing on the management of CCB overdose. We will break this section down into initial resuscitation, the role of gastrointestinal decontamination, and specific medial therapies.

Let’s start with the ABC approach and initial resuscitation. What are some key management pearls?

An immediate consult with Poison control center is a must: PCC can help guide monitoring, investigational studies as well as patient management.

Empiric use of Glucagon 5-15mg IV may be warranted when patient presents with hypotension/bradycardia. Glucagon promotes calcium entry into cells via stimulation of a receptor that is considered to be separate from adrenergic receptors.

• Circulation is the main focus of the treatment of calcium channel blocker (CCB) exposures. Hypotension and bradycardia can be profound and refractory even to maximal treatment.
• Judicious use of Intravenous (IV) fluids, as well as vasopressors, are the initial therapy for hypotension, and atropine for the initial treatment for bradycardia, but both may be insufficient.

Our patient in our case maintained clear mental status despite hypotension and bradycardia. However, we need to reassess these patients frequently, as precipitous deterioration is common, and many will eventually require intubation and mechanical ventilation. With the exception of nimodipine, calcium channel blockers have poor CNS penetration. Therefore, drowsiness, seizures, or altered mental status in the absence of hemodynamic collapse should alert the physician to the possibility of co-ingestions.

For patients with CCB overdose, is there a role for orogastric lavage?

• Oro-gastric lavage and activated charcoal may be necessary for patients who present within one to two hours, however, make sure to use caution in a patient who has borderline mental status and who may not be able to protect their airway.
• Another clinical pearl to consider is that the vagal stimulation from orogastric lavage may exacerbate CCB-induced hypotension and bradycardia.

Let’s transition and talk about specific medical therapies. In diving deep into the literature, we will talk about the role of catecholamines/vasopressors, Atropine, IV Ca, Glucagon, Insulin & Dextrose, and Lipid emulsion therapies.

What vasopressors/catecholamines are used in CCB?

• Direct-acting vasopressors such as norepinephrine/epinephrine infusion is preferred in CCB. Angiotensin II (Giapreza) -a vasoconstrictor can be considered in patients 18 years of age and above.

How does atropine help in CCB overdose?

• Atropine is a muscarinic antagonistic and thus should be administered to any patient with symptomatic bradycardia after CCB. Pediatric dosing is 0.02 mg/kg IV, with a minimum dose of 0.1 mg to avoid the paradoxical bradycardia that may result from very small doses of this medication.
• What about IV Calcium?

• Calcium salts are often used to overcome the cardiovascular effects of CCBs.
• As calcium channel blockers as the name implies, inhibit calcium it is important for us to understand that CCB poisoning interferes with both the serum concentration and the intracellular handling of calcium.
• Anecdotally high-dose continuous infusion of calcium should be administered — after bolus dosing, a reasonable infusion of Ca Cl to consider is 0.5 mEq of calcium/kg per hour. Close monitoring of the serum or ionized calcium concentration (measurements every two hours) and serial electrocardiograms (ECGs) are necessary to avoid clinically significant hypercalcemia, which has been reported with intensive calcium therapy. The use of an aline for serial labs and hemodynamic monitoring is essential.
• What about Glucose and Insulin:
• High dose insulin (1-10U/KG/hr after a 1U/kg bolus dose) is required in CCB along with dextrose which helps to counteract the hypoglycemia. Hypokalemia can occur due to a shift in K intracellularly and requires close monitoring. It generally takes approximately 30 minutes to see the effects from HIE. The main beneficial effect is on myocardial function (ie, ejection fraction and cardiac output), with subsequent improvement in blood pressure and perfusion although improvement in cardiac rhythm has also been reported.
• Investigational therapies: use of methylene blue (1-2mg/kg), lipid emulsion can be tried as a last resort in those with severe hemodynamic issues and can be used even if the patient is not in cardiac arrest.
• Please visit our episode entitled PICU Applications of Lipid Emulsion Therapy. The use of lipids is controversial however in general: an IV bolus of 1 to 1.5 mL/kg is given over one minute of a 20 percent lipid emulsion solution. If there is no response, the same dose may be repeated in cases of cardiac arrest every three to five minutes for a total of three bolus doses. Following the initial bolus, an infusion is started at a rate of 0.25 to 0.5 mL/kg per minute until hemodynamic recovery occurs. The infusion is generally maintained for 30 to 60 minutes. The infusion rate may be increased if the patient's blood pressure drops.
• 
  
• 
  
• Procedures that may be required in CCB include: 1) A transvenous pacemaker may be placed if the transthoracic cutaneous pacer fails to capture in the face of symptomatic bradycardia. Pacing may decrease the need for pressors in a patient who may not tolerate a positive cardiac inotrope because of cardiac ischemia, although this likely is not a concern in children. Cardiac pacing is typically required for 12-48 hours.
• 
  
• 2) Extracorporeal membrane oxygenation (ECMO) has also been attempted in patients who have hypotension refractory to all pharmacologic therapies.
• 
  
• Rahul what are Key objective take-aways from today’s episode:

1. Hypotension & bradycardia is a life-threatening toxidrome that is related to circulatory collapse and poor cerebral perfusion.
2. Differential includes:
3. CCB
4. BB
5. Digoxin
6. Clonidine
7. CNS depressants
8. A stepwise approach to CCB includes — close monitoring of ABCs, and in severely symptomatic patients: IV boluses of isotonic crystalloid, IV calcium salts, IV glucagon, IV high-dose insulin and glucose, IV vasopressor (eg, norepinephrine), and IV lipid emulsion therapy in refractory cases.

This concludes our episode on Approach to Calcium Channel Blockers. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as...

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.

I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.

Here's the case:

A 6-year-old child with a known h/o craniopharyngioma who has been endocrinologically intact with exception of needing thyroid replacement was admitted to the PICU prior to craniotomy to proceed with further tumor resection as well as the removal of a secondary cyst impacting his brainstem. The patient is receiving Keppra for seizures and per mother, he has recently been significantly more sleepy at school.

On POD Op day 5: the PICU the bedside nurse notices increased urine output (6cc/kg/hr to as high as 10cc/kg/hr). Initially, there was an increase in Na to 157mEq/L within 48-72 hours the serum Na dropped to 128mEq/L

To summarize key elements from this case, this patient has:

• Increase UOP
• Rapidly increasing Na initially followed by a drop
• All of which brings up a concern for Na abnormality post craniotomy

In today’s episode, we will be breaking down all things Sodium & the Brain. We will discuss diagnostic & management frameworks related to three pathologies:

1. Central Diabetes Insipidus
2. Syndrome of inappropriate Anti-Diuretic Hormone or SIADH
3. Cerebral Salt Wasting

These diagnoses can certainly be seen individually inpatients or as a spectrum of diseases — as we go through each of these diagnoses, pay particular attention to patient characteristics and lab abnormalities. Namely, serum sodium, serum osm, and urine osm.

To build the fundamentals, lets first start with classic nephrology saying: Serum Na represents Hydration

This takes us into a brief review of normal physiology — talking about three important hormones:

1. ADH
2. Aldosterone
3. Atrial Natriuretic Peptide (ANP)

Let’s go through a quick multiple-choice question.

A patient is recently started on DDAVP for pan-hypopituitarism. The medication acts similarly to a hormone that is physiologically synthesized in which of the following from which are in the body?

A. Paraventricular Nucleus of the Hypothalamus

B. Supraoptic Nucleus of the Hypothalamus

C. Anterior Pituitary

D. Vascular Endothelium

The correct answer here is B the Supraoptic Nucleus of the Hypothalamus. Remember that ADH is synthesized in the hypothalamus and released from the posterior pituitary.

What are the physiologic actions of ADH?

ADH Increases H2O permeability by directing the insertion of aquaporin 2 (AQP2) H2O channels in the luminal membrane of the principal cells. Thus, as we will see with Central Diabetes insipidus, in the absence of ADH, the principal cells are virtually impermeable to water.

Let's talk about our next hormone, aldosterone. What are the important physiologic considerations?

• Aldosterone is secreted from the adrenal cortex as a byproduct of the RAAS.
• Aldosterone increases Na+ reabsorption by the renal distal tubule, thereby increasing extracellular fluid (ECF) volume, blood volume, and arterial pressure.
• It also helps in secreting K and H. This physiology is applied directly at the bedside when we have patients in the ICU who have a contraction alkalosis secondary to diuretics. The increase in aldosterone as these patients lose free water from their Lasix administration results in hypokalemia and metabolic alkalosis.

Alright, what about the third hormone, ANP?

• Atrial natriuretic peptide (ANP) is released from the atria in response to an increase in blood volume and atrial pressure.
• ANP causes relaxation of vascular smooth muscle, dilation of arterioles, and decreased TPR.
• causes increased excretion of Na+ and water by the kidney, which reduces blood volume and attempts to bring arterial pressure down to normal.

As ANP causes natriuresis, diuresis, and inhibition of renin, you can consider this hormone as having a complementary & opposite effect to ADH and aldosterone.

Alright, now that we have the basics, let's talk about our index case presentation, central diabetes insipidus, can you illustrate the key diagnostic features of this disease?

• Central diabetes insipidus (CDI) is an important cause of hypernatremia in the intensive care setting and can be seen in primary brain lesions, traumatic brain injury, or as a harbinger of brain death.
• CDI results from inadequate ADH secretion. Children in the intensive care setting typically present with abrupt polyuria and free water diuresis.

What are common triggers for CDI?

• Traumatic brain injury, brain tumors, pituitary surgery (i.e. postoperative craniopharyngioma resection), central nervous system infections, and cerebral hemorrhages or infarcts.
• CDI occurs most commonly in the setting of brain death.

 Because patients with CDI can conserve sodium appropriately, they typically do not manifest signs of volume depletion unless the diagnosis is delayed. Thus CDI is a cause of euvolemic hypernatremia.

Absolutely, actually, in CDI the urine osmolality is typically less than the plasma osmolality. These patients have about >4 mL/kg/hr of urine output.

What is the management of CDI?

• CDI includes the correction of free water deficit and the administration of the ADH synthetic analog desmopressin acetate (dDAVP). In a critically-ill patient, a vasopressin infusion may be needed for the rapid increase in UOP and serum Na. An advantage of vasopressin is the “quick on-off effect”
• Desmopressin can be administered subcutaneously, intranasally, or intravenously. The dosing varies by the route of administration and can be thought of as the 1-10-100 rule.
• IV 1mcg
• IN 10mcg (one puff = 10mcg)
• PO 100mcg
• In critically ill patients, edema and peripheral vasoconstriction may preclude effective subcutaneous administration therefore intravenous administration of dDAVP or a continuous vasopressin infusion may be required.

Alright, so you gave the patient with presumed CDI a dose of DDAVP. What will you expect?

• Patients with central diabetes insipidus will typically have a reduction in urinary output and a greater than 50% increase in urine osmolality in response to the first dose of dDAVP.
• At times we are measuring their urine output in mL/kg/hr so if a patient is on a continuous vasopressin infusion for DI, titrating to a UOP of 1-2 mL/kg/hr can be appropriate.

Rahul why do you think in our patient with high UOP and a high serum Na, the serum Na suddenly dropped in 48 hours?

There are two possibilities. Either patient has received DDAVP or more likely patient is having a Triphasic Response as many patients undergoing pituitary surgery do (DI within 2-4 days, followed by SIADH for 2-5 days, and a return to DI), which sometimes can be difficult to treat.

Most patients with CP already have pituitary hormone deficiencies at the time of diagnosis, which is more common in children than adults. Approximately 70% of children had growth hormone (GH) deficiency, followed by gonadotropin deficiency (51.7%), central diabetes insipidus (CDI, 28.6%), and thyroid-stimulating hormone (TSH) deficiency (21.9%), and adrenocorticotrophic hormone (ACTH) deficiency (12.5%).

The course of postoperative CDI can be transient, permanent, or a component of the triphasic pattern.

Pradip, can you highlight the triphasic response a bit more?

• In the first phase of the triphasic pattern, there is an acute increase in hypo-osmolar urine output within 24–48 h following surgery due to antidiuretic hormone (ADH) deficiency resulting from traumatic edema of the neurons, axonal shock due to impairment of vascular supply, and/or pituitary stalk transection.
• The patients have a tendency toward hypernatremic dehydration during this phase, which lasts approximately 1–7 days. At this phase, appropriate fluid replacement is required to prevent water loss and hypernatremic dehydration.
• However, low-dose diamino D-arginine vasopressin (desmopressin; dDAVP) can be used to decrease fluid intake/output. dDAVP replacement dose should be titrated with caution because its long half-life during this phase may complicate the subsequent hyponatremic phase of the triphasic response.

Let’s transition to the other extreme, and that is SIADH — syndrome of too much ADH. What are some common etiologies?

• SIADH can occur due to a variety of illnesses, but most often occurs due to central nervous system disorders, pulmonary disorders, and medications. As this episode is all things brain and salt related, common CNS diagnosis that can lead to SIADH are:
• Meningitis, encephalitis
• Neoplasms
• Post-pituitary surgery
• Hydrocephalus
• Head Trauma

We will be reviewing specific electrolyte disorders in future episodes however please remember that hyponatremia like SIADH typically develops when a relative excess of free water is accompanied by an underlying condition that impairs the kidney’s ability to excrete free water. In SIADH, ADH secretion occurs independently of serum osmolality and intravascular volume status.

Interestingly, SIADH is essentially a diagnosis of exclusion. Before SIADH can be diagnosed, diseases causing decreased effective circulating volume, renal impairment, adrenal insufficiency, and hypothyroidism must be excluded.

Clinically, what will we see?

• The hallmarks of SIADH are:
• mild volume expansion with low to normal plasma concentrations of creatinine, urea, uric acid, and potassium
• impaired free water excretion with normal sodium excretion which reflects sodium intake
• hyponatremia which is relatively unresponsive to sodium administration in the absence of fluid restriction.

If left uncorrected, SIADH can lead to severe hyponatremia (plasma Na <120 mEq/L) - leading to seizures.

To close out this topic, how would you approach the management of SIADH?

• SIADH is usually of short duration and resolves with treatment of the underlying disorder and discontinuation of the offending medication.
• Additionally, fluid restriction is the cornerstone of therapy for SIADH.
• However, fluid restriction results in slow correction of hyponatremia and is frequently impractical in infants who receive most of their nutrition as liquids.

Finally, let’s talk about Cerebral salt wasting. How can we compare and contrast CSW and SIADH?

• In the setting of CNS injury or following a neurosurgical procedure, hyponatremia is usually attributed to SIADH, a condition whose hallmark is euvolemia to mild hypervolemia, with the cornerstone of management being fluid restriction.
• More recently it has become apparent that an increasing number of neurosurgical patients with hyponatremia can have CSW a condition whose hallmark is renal sodium loss leading to extracellular volume depletion.

So to summarize patients with CSW and SIADH can both be hypoNa in the setting of brain injury however patients with CSW are hypovolemic relative to patients with SIADH who have a euvolemic hypoNa.

What is the pathogenesis of CSW?

• The pathogenesis of CSW is not completely understood, but it appears to be due to the release of natriuretic peptides, such as an atrial natriuretic peptide. As we reviewed in our physiology discussion, ANP helps us with three things:
• hemodynamic effects leading to an increased GFR
• inhibition of the renin
• Inhibition of the secretion and action of ADH
• And, just to summarize, the key distinguishing feature between CSW and SIADH is extracellular volume depletion. You can establish this assessment via serial monitoring of UOP, clinical exam, and CVPs.

Pradip, any other clinical pearl regarding CSW?

• Yes, so when you provide NS infusion to a patient, let's say with SIADH — it should be adequate prophylaxis to prevent hypoNa (i.e. a sodium <130 meQ/L)
• However, If clinically significant hyponatremia develops inpatient with a CNS disorder receiving only normal saline, then the diagnosis of CSW should be strongly considered.

How do we manage these patients?

• The hallmark pearl is to expand their intravascular space.
• This can be achieved by normal saline, followed by sufficient quantities of normal saline and 3% NaCl to main fluid balance and normal serum sodium. There have been studies that have advocated the administration of fludrocortisone as aldosterone production is relatively decreased in CSW.

Ok, Rahul, do you mind summarizing today’s episode?

This concludes our episode on All Things Sodium & the Brain in the PICU. We hope you found value in our short, case-based podcast. We welcome you to share your feedback, subscribe & place a review on our podcast! Please visit our website picudoconcall.org which showcases our episodes as well as our Doc on Call management cards. PICU Doc on Call is co-hosted by myself Dr. Pradip Kamat and Dr. Rahul Damania. Stay tuned for our next episode! Thank you!

• References:
• Bereket A: Postoperative and Long-Term Endocrinologic Complications of Craniopharyngioma. Horm Res Paediatr 2020;93:497-509. doi: 10.1159/000515347
• Prete A, Corsello SM, Salvatori R. Current best practice in the management of patients after pituitary surgery. Therapeutic Advances in Endocrinology and Metabolism. March 2017:33-48. doi:10.1177/2042018816687240