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Julie Brown, MD Midwest Pediatric Hospital Medicine Conference June 12, 2010

Clinical Conundrum. Julie Brown, MD Midwest Pediatric Hospital Medicine Conference June 12, 2010. History. 4 week old male with a 1 day history of poor feeding and being more sleepy, fussy, sweaty, and clammy. Infant found floppy and unresponsive with blue lips and hands.

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Julie Brown, MD Midwest Pediatric Hospital Medicine Conference June 12, 2010

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  1. Clinical Conundrum Julie Brown, MD Midwest Pediatric Hospital Medicine Conference June 12, 2010

  2. History • 4 week old male with a 1 day history of poor feeding and being more sleepy, fussy, sweaty, and clammy. Infant found floppy and unresponsive with blue lips and hands. • Presented to outside ED with cyanosis, respiratory distress, delayed cap refill, sat 80%. • Two weeks prior he was hospitalized locally for fever and RSV (late May). Septic workup negative. Hospitalized for 7 days due to oxygen requirement and increasing WBC that stabilized on the day of discharge. • The infant was seen by the PMD the day prior to this presentation (3 days after hospital DC) and had improved, per mom.

  3. Birth History: Term, vaginal delivery 7lb 12oz No complications Allergies: NKDA Imm: Hep B given Medications: Xopenex SH: Lives with parents, maternal grandparents and 5 year old sibling. No daycare. All adults smoke. No reported ill contacts. No recent travel. FH: no history of heart or lung disease, no leukemia, unremarkable

  4. ED Course • Suctioned and oxygen applied, sat 98%, pink • CBC and blood culture obtained • 10 mL/kg NS bolus, 50 mg/kg IV ceftriaxone prior to transfer via helicopter to Children’s Emergency Department • Upon arrival Temp 38.1 C, Pulse 185, glucose 35. coarse breath sounds with retractions and grunting, delayed cap refill, mottled. Septic workup completed, LP done. Given IV cefotaxime, dextrose, and additional 20ml/kg NS, and admitted to inpatient unit for further care.

  5. Laboratory CBC: WBC 57.8, Hgb 11, Plat 624, Segs 49, Bands 4, Lymph 38 BMP: Na 124, K 5.7, Cl 92, CO2 27, BUN 35, Creat 0.3, Ca 9.9, Gluc 35 CSF WBC 124, RBC 89, many immature WBC and 55% NRBC, 31% lymphs, 18% mono/macro Glucose 37, Protein 78 UA: trace protein, otherwise negative LFT: AST 60 (20-50), ALT 66 (20-60), Alb 3.0 (3.6-4.6), LDH 1425 (425-975), Uric Acid 2.4 Serology: ESR 1, CRP 0.6 Coags normal

  6. Perihilar streaking and hyperinflation, heart size normal CXR

  7. Physical Exam Temp: 36.9 C, Resp: 32, BP 93/65, Pulse 176, sat 95% on ½ liter NC Wt. 4.6 kg General: alert with spontaneous movement, no cry HEENT: NCAT, AFSF, PERRL, no conjunctivitis or icteric sclera, mucous membranes tacky, OP clear without erythema, TMs grey bilaterally Neck: supple, no lymphadenopathy Chest: mild distress, crackles throughout, no wheeze, equal breath sounds CV: tachycardia, capillary refill 3 seconds Abd: soft, non-tender, no HSM, no mass GU: normal male, testes descended bilat Ext: no joint swelling or limited movement Skin: pale, no rash except neonatal acne on chin, multiple bruises from IV attempts, no active bleeding, LP site clean Neuro: fair tone with strong suck and grasp, no assymetry or weakness, normal DTRs

  8. CC: cyanosis, floppy HPI: 4 week old male with 1 day history of poor feeding, decreased activity, fever, respiratory distress PMH: Recent admit for RSV, sepsis eval, report of increasing WBC count Physical Findings: leukocytosis, CSF pleocytosis, hypovolemic shock, and hypoglycemia. coarse lungs, dry mucous membranes, tachycardia Differential Diagnosis

  9. Clinical Course • On arrival to the inpatient unit he was given 40 ml/kg of NS to help correct hyponatremia and hypovolemia. Acyclovir was added in addition to vancomycin and ceftriaxone. • Within the first 12 hours of hospitalization he had worsening respiratory distress and perfusion and was transferred to the ICU and intubated (14 days) • Infectious Disease was consulted and supported diagnosis of meningitis in light of CSF pleocytosis, and were suspicious of sepsis due to shock presentation, but most cultures were obtained after antibiotics

  10. Clinical Course cont. • (ID cont.) There was also high suspicion of viral etiology so multiple viral tests were obtained as well as pertussis testing and azithromycin was started pending results. • Pathology reviewed CSF WBC and peripheral smear: mixed granulocytic and lymphocytic leukamoid changes. No evidence of leukemia. did not see blasts or cells suggestive of oncologic process • WBC slowly returned to normal over next 7 days

  11. Microbiology • Blood culture (pre-antibiotic from outside hospital) was lost in transit • Blood culture (post-antibiotics) negative • CSF culture (post-antibiotics) negative • Urine culture (post-antibiotics) negative • Viral eye, nasal, rectum negative • CSF Enterovirus PCR negative • CSF Herpes PCR negative • Respiratory Viral Panel and Pertussis pending

  12. On HD #5 respiratory viral testing returned positive rhinovirus/enterovirus. ID felt this was likely etiology of CSF WBC but infant completed 7 days of antibiotics due to pre-treatment. On HD #7, final day of azithromycin treatment, pertussis PCR returned positive which was likely explanation for leukocytosis and respiratory symptoms. He had issues with hypoxia, feeding difficulties and abstinence syndrome but was finally discharged after a month in the hospital Clinical Course cont.

  13. In prevaccination era, pertussis was a leading cause of infant death. Recent increase in number of cases by 2300% between 1976 and 2005 significant cause of morbidity and mortality in infants younger than 2 years. Differential diagnosis of protracted cough with cyanosis or vomiting, persistent rhinorrhea, and marked lymphocytosis Pertussis

  14. Bordetella pertussis: aerobic, nonmotile, gram-negative coccobacillus attaches to/multiplies on respiratory epithelium Transmission is only human to human by aerosol highly contagious. 80-90% of susceptible individuals who are exposed develop the disease. late summer and early fall. Pathophysiology

  15. Overall infant mortality rate is 2.4 per 1 million live births.  CDC reported 39 deaths from pertussis in 2005; 32 (82%) occurred in infants <3 months.  World Health Organization (WHO) estimates that 294,000 children died from pertussis worldwide in 2002. Risk factors include the following: Nonvaccination in children Contact with an infected person Epidemic exposure Pregnancy Mortality/Morbidity

  16. occurs predominantly in ages 3 months to 5 years, >70% of cases reported in children <5 years. lack of maternal immunity transfer 10-15% of all cases occur in infants <6 months, with >90% of all death in same age group. growing majority of cases are now in 10 years and older, leading to increased booster recommendations. Natural disease does not provide lifelong immunity as earlier thought. 3 injections of cellular/acellular vaccine provides up to 12 years of protection. Age

  17. 3 stages: incubation, catarrhal, and paroxysmal. asymptomatic incubation period lasts 7-10 days. catarrhal stage, lasts 2-7 days. Minimal or no fever, Rhinorrhea, Anorexia, Mild but increasing cough paroxysmal stage, lasts 1-8 weeks. paroxysms of coughing, provoked by feeding (in infants) and exertion. The inspiratory gasp or whoop eventually develops, especially in those aged 6 months to 5 years. Clinical History

  18. Clinical History cont. • Infants younger than 6 months often with cyanosis and apneic spells. • Vaccinated adults usually develop only prolonged bronchitis without a whoop, whereas unvaccinated adults are most likely to have whooping and posttussive emesis. • About 12-32% of adults with persistent cough (>2 wk) have pertussis. On average, they wait a median of 3 weeks before seeking treatment.

  19. Blood work Lymphocytosis is often profound (>70% of the total WBC count), especially in children. The WBC count often increases to 20-40,000 or even 100,000 cells/mm2. In adults, especially those that had been vaccinated, lymphocytosis is rare. Cultures A definitive culture diagnosis is not always possible. Laboratory Findings

  20. Laboratory Findings • Direct fluorescent antibody (DFA) studies • results within minutes, its use is not recommended because of both low sensitivity and low specificity. • Results are positive in 40-80% of patients so is commonly used to confirm cases. • Polymerase chain reaction (PCR) testing to detect DNA • PCR testing may reveal <10 organisms per swab sample. • high sensitivity • PCR or positive culture is the case definition for reporting pertussis to the CDC or WHO

  21. Infants should be observed for apnea, cyanosis, or hypoxia. Try to isolate patients from others (especially infants) for 4 weeks, especially until 5-7 days of antibiotic therapy is completed when transmission is considerably decreased. considerations for admission: Age younger than 1 year Pneumonia Apneic or cyanotic spells or hypoxia Moderate-to-severe dehydration Treatment

  22. Treatment • prophylaxis for household and close contacts is recommended. • Erythromycin 50 mg/kg/d divided 4 times a day (qid) for 14 days • Alternative: Azithromycin 10 mg/kg on day 1 then 5 mg/kg on days 2 through 5. • If the patient is allergic to erythromycin/azithromycin, use trimethoprimsulfamethoxazole (TMP-SMZ).

  23. prevention of pertussis through immunization is vital. Herd immunity does not completely protect unvaccinated children. Measurable antibody wanes after 3-5 years and is not measurable after 12 years Vaccination is recommended with DTaP at the ages of 2, 4, 6, and 15-18 months, and 4-6 years of age. A booster with Tdap is recommended in adolescents or adults requiring tetanus immunization who did not have an adolescent booster. Exploring means of preventing disease transmission to infants including maternal vaccination to provide passive antibody and vaccinating at birth Vaccination

  24. Questions?? Enjoy your Summer!

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