Marie Gauthier

Timing and predictors of death in pediatric patients with multiple organ system failure.

ObjectivesTo describe the timing of onset of organ system failure, multiple organ system failure diagnosis, and the subsequent death in children admitted to a pediatric intensive care unit (ICU). Second, to identify independent risk markers of death in pediatric patients with multiple organ system failure. DesignReview of a database. SettingPediatric ICU within a tertiary care center. PatientsWe analyzed the pediatric ICU course of 777 consecutive patients aged <18 yrs. Measurements and Main ResultsEighty-five (10.9%) of 777 children had multiple organ system failure, defined as the simultaneous occurrence of at least two organ system failures. Of 85 children, 37 (43.5%) were postoperative cardiac surgery patients and 48 (56.5%) patients were in the ICU for other reasons. The diagnostic criteria for multiple organ system failure were met on the day of admission by 73 (86%) of 85 patients. The maximum number of organ system failures occurred within 72 hrs in 74 (87%) children. The mortality rate for all patients with multiple organ system failure was 50.6%. Thirty-eight (88.4%) of deaths occurred within 7 days after the diagnosis of multiple organ system failure. Survival analysis was comparable for both postoperative cardiac surgery patients and patients with other diagnoses. Multivariate analysis identified three factors as independent risk markers of death in pediatric patients with multiple organ system failure: maximum number of simultaneous organ system failures during the pediatric ICU stay: odds ratio, 55.9 (95% confidence interval, 7.9 to 396.1); age ≤12 months: odds ratio, 17.1 (95% confidence interval, 1.8 to 158.7); and the Pediatric Risk of Mortality (PRISM) score on the day of admission: odds ratio, 1.25 (95% confidence interval, 1.1 to 1.5). ConclusionsThe mortality rate associated with multiple organ system failure in pediatric patients is high. The maximum number of simultaneous organ system failures during pediatric ICU stay, age ≤12 months, and the PRISM score on the day of admission are independent risk markers of death. Diagnosis of multiple organ system failures, development of maximum number of organ system failures, and deaths occur remarkably early after pediatric ICU admission; the rationale for using prophylactic therapy under such circumstances is unclear. (Crit Care Med 1994; 22:1025–1031)

Neurologic Crises in Hereditary Tyrosinemia

Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconis syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.

Frequency of upper gastrointestinal bleeding in a pediatric intensive care unit.

ObjectiveTo determine the frequency of upper gastrointestinal (GI) bleeding in pediatric ICUs. DesignProspective, descriptive study. SettingPediatric ICU in a university hospital. PatientsAll children admitted to a pediatric ICU over a 55-wk period. InterventionNone. Measurements and Main ResultsUpper GI bleeding was considered to be present if there was an episode of hematemesis or if any amount of blood was seen in drainage from a nasogastric tube. Sixty-three (6.4%) upper GI bleeds were detected among 984 patients: 5.2% in 698 patients who did not receive upper GI bleeding prophylaxis, and 9.4% in 286 patients who did receive some prophylaxis. Density was defined as the number of events/1000 days patient. The mean density was 10.8 GI bleeding episodes/1000 days patient in a pediatric ICU. A multivariate analysis detected four independent risk factors or risk markers for upper GI bleeding: high Pediatric Risk of Mortality score, coagulopathy, pneumonia, and multitrauma. Age, sex, hepatic and respiratory failures were identified as confounding variables. An upper GI bleeding episode was defined as being clinically important if hypotension, death, or transfusion occurred within 24 hrs after the bleeding. There were four clinically important GI bleeding epidodes. All were caused, at least in part, by a coagulopathy. The GI bleeding was associated with a need for transfusion in four children, and with hypotension in two. ConclusionsThe frequency of upper GI bleeding is substantial, but the rate of occurrence of clinically important upper GI bleeding is low, even in a pediatric ICU where most patients do not receive any prophylaxis. (Crit Care Med 1992; 20:35)

Admissions to a pediatric intensive care unit for status epilepticus: a 10-year experience.

ObjectiveTo characterize the etiology, course, and prognosis in children admitted to a pediatric intensive care unit (ICU) for status epilepticus. DesignRetrospective, descriptive study. SettingPediatric ICU in a university hospital. PatientsOne hundred forty-seven children admitted with status epilepticus. InterventionsNone. Measurements and Main ResultsStatus epilepticus was defined as a prolonged (>30 mins) or repeated tonic or tonic-clonic seizure with a persistent altered state of consciousness. Over 10 yrs, 147 children 0 to 16 yrs of age (median 1; mean 3.4 ± 3.9 [SD]) were admitted to a pediatric ICU for, or with, 153 episodes of status epilepticus. Status epilepticus was caused most often by epilepsy (n = 52), atypical febrile convulsions (n = 21), bacterial meningitis (n = 20), encephalitis (n = 20), intoxication (n = 8), or a metabolic disorder (n = 12). Two infants, 1 and 3 months of age, and a patient with intoxication by isponiazid, responded to pyridoxine. Among 114 previously normal children, 34 patients displayed a new neurologic problem on discharge from the ICU, among whom, 68% (23/34) still had some neurologic abnormality 1 yr after the episode of status epilepticus. Nine patients died during their ICU stay, mostly from underlying disease rather than from the status epilepticus itself. A normal neurologic status before status epilepticus and age >4 yrs seem to be markers of good prognosis, while encephalitis and meningitis appear to be markers for morbidity and mortality. ConclusionsMost cases of status epilepticus were caused by epilepsy, atypical febrile seizure, encephalitis, meningitis, or metabolic disease. The mortality rate during the ICU stay was 6%. The prognosis was good in most surviving cases, more so if the neurologic development of the child was normal before the status epilepticus. (Crit Care Med 1994; 22:827–832)

Prophylaxis of upper gastrointestinal bleeding in intensive care units: a meta-analysis.

A meta-analysis was performed of 15 randomized studies on the prophylaxis with cimetidine and/or ant-acids of upper GI bleeding acquired in the ICU. There were eight comparisons of a group receiving cimetidine with a control group, nine comparisons of a group receiving antacids with a control group, and ten comparisons of a group receiving cimetidine with a group receiving antacids. The incidence of upper GI bleeding ranged from 3.4% to 52.7% among 866 control patients who received either a placebo or no prophylaxis. In five of eight comparisons, cimetidine was significantly more effective than no treatment or a placebo to prevent occult and overt upper GI bleeding; the typical odds ratio was 0.32 (95% confidence interval 0.21 to 0.49). In six of nine comparisons, antacids were significantly more effective than no treatment or a placebo; the typical odds ratio was 0.12 (0.08 to 0.19). Finally, antacids were significantly more effective than cimetidine in two of ten comparisons; the typical odds ratio was 1.61 (0.97 to 2.65). However, weaknesses in the study designs, heterogeneity of treatment effects, the lack of strength of the accumulated evidence, and the fact that no utility has been shown in terms of reducing morbidity (shock, need for transfusion) or mortality, prevent any definitive conclusion in regard to compulsory use of upper GI bleeding prophylaxis for ICU patients.

Incidence of infection related to arterial catheterization in children: a prospective study.

The incidence of infection related to arterial catheterization has not been studied in critically ill children, using systematic catheter cultures. We studied prospectively 68 children in whom 70 arterial catheters were inserted. After the aseptic catheterization procedure, no component of the system was changed. The insertion site was inspected daily for signs of inflammation. Upon removal, catheters were cultured using a semiquantitative method. Blood and infusion fluid specimens were also cultured if septicemia was clinically suspected. Mean duration of catheterization was 59 +/- 6 (SE) h. In our series, all catheter and infusion fluid cultures were negative. Local inflammation was not predictive of catheter tip infection and correlated poorly with duration of catheterization (r = 0.2). In our experience, the incidence of infection related to arterial catheterization is low. Routine change of infusion fluid, tubing, dressing and insertion site as well as systematic catheter culture in the absence of fever appears unwarranted.

Treatment of Urinary Tract Infections Among Febrile Young Children With Daily Intravenous Antibiotic Therapy at a Day Treatment Center

Objective. Urinary tract infections (UTIs) are common among infants and toddlers. Children can be treated effectively with short courses (2–4 days) of intravenous (IV) therapy followed by oral therapy. If IV therapy is chosen, use of once-daily dosing may allow outpatient management instead of hospital admission. However, no description of ambulatory treatment with IV antibiotics of UTI among febrile children has been reported to date. We aimed to describe the feasibility and complications of outpatient management with IV antibiotics of UTI among febrile children, at the day treatment center (DTC) of a tertiary-care pediatric hospital. Methods. Between April 1, 2002, and March 31, 2003, a prospective cohort of patients 3 months to 5 years of age who were examined in the emergency department (ED) and diagnosed as having presumed febrile UTI were treated according to a clinical protocol. Patients were treated at the DTC unless they met exclusion criteria, in which case they were hospitalized. The DTC was open 7 days per week, including holidays, from 8:30 am to 4:30 pm. At the DTC, patients were initially treated with a daily dose of IV gentamicin, until the child had been afebrile for at least 24 hours, and with oral amoxicillin, until preliminary urine culture results were available. Children allergic to penicillin received gentamicin only. IV antibiotics were administered through peripheral IV access; the IV catheter’s patency was maintained with injection of 50 U of heparin once daily throughout the treatment period. Parental satisfaction with the DTC experience was assessed with an anonymous, self-administered questionnaire. Results. Two hundred ninety-one episodes of presumed febrile UTI were diagnosed in the ED, of which 212 (72.9%) were sent to the DTC. There were 71 hospital admissions (24.4%); in 9 of these instances, the child was admitted because parents refused or were unable to comply with DTC treatment. Adherence to the treatment protocol in the ED was excellent; in 92.1% of presumed febrile UTI episodes (268 of 291 episodes), the patient was referred to the appropriate setting for treatment. In 8 instances, patients who met an exclusion criterion were sent to the DTC. They should have been hospitalized, according to the protocol. At the DTC, a final diagnosis of UTI was made in 178 of the 212 episodes (84%). Patients treated at the DTC, with a final diagnosis of UTI, had a median age of 12.0 months (range: 3–68 months), and their mean initial temperature was 39.2°C (SD: 1.1°C). Patients were afebrile by 24 hours in 52% of UTI episodes and by 48 hours in 82%. Minor problems with IV access occurred in 9.0% of cases. The duration of IV antibiotic therapy at the DTC was 1.9 days (SD: 0.9 day). The mean number of visits to the DTC, including appointments for renal ultrasound and voiding cystourethrography evaluations, was 3.5 (SD: 0.9). Parents were present at all scheduled visits in 98.9% of cases. Four patients needed to be hospitalized from the DTC, but in only 1 case was hospital admission related to UTI treatment. Four patients with UTI treated in the DTC had positive blood cultures, 2 with Escherichia coli (both successfully treated at the DTC) and 2 with contaminants. For 4 children treated at the DTC, UTI was caused by gentamicin-resistant E coli. One patient became afebrile within 24 hours after treatment initiation with IV gentamicin; he was then treated with oral cefixime. A second patient was treated with IV ceftriaxone, administered at the DTC once culture results were available, and remained febrile for <72 hours. The last 2 patients were hospitalized; one, who was also allergic to cephalosporins, had been febrile for 72 hours at the time of hospitalization (once hospitalized, he was treated with IV amikacin), and the other was admitted to the hospital for an unrelated problem, namely, scalp cellulitis. None of these 4 patients was initially bacteremic or became bacteremic during the treatment period. Repeat urine culture was performed within 14 days after treatment initiation in 146 instances, and results were negative in all cases. At telephone follow-up assessments 14 days after discharge, no patient had been rehospitalized because of UTI. Successful treatment at the DTC (defined as attendance at all visits, normalization of temperature within 96 hours, negative control urine cultures, if performed, and absence of hospitalization from the DTC) was observed in 96.6% of the 178 UTI episodes. Overall adherence of physicians to the protocol at the DTC was 87.1% (95% confidence interval: 82.2-92.0%). One hundred seventy-two satisfaction questionnaires were returned and revealed good, very good, or excellent parental satisfaction in 98.8% of cases. Conclusions. Our data show that ambulatory treatment with IV antibiotics, at a DTC, may be used for at least three-fourths of UTIs among febrile children 3 months to 5 years of age. It is safe and feasible and appears very satisfactory to parents. Although ambulatory treatment with IV antibiotics is more invasive than oral therapy during the initiation of UTI treatment, it ensures almost full compliance, allows close medical supervision, and facilitates investigations related to the UTI. It is an interesting alternative to hospitalization.

Urinary Tract Infections in 1- to 3-Month-Old Infants: Ambulatory Treatment With Intravenous Antibiotics

OBJECTIVE: The goal was to examine the feasibility of outpatient management for 1- to 3-month-old infants with febrile urinary tract infections. METHODS: A cohort study was performed with all children 30 to 90 days of age who were evaluated for presumed febrile urinary tract infections in the emergency department of a tertiary-care pediatric hospital between January 1, 2005, and September 30, 2007. Patients were treated with intravenously administered antibiotics as outpatients in a day treatment center unless they met exclusion criteria, in which case they were hospitalized. RESULTS: Of 118 infants included in the study, 67 (56.8%) were admitted to the day treatment center and 51 (43.2%) were hospitalized. The median age of day treatment center patients was 66 days (range: 33–85 days). The diagnosis of urinary tract infection was confirmed for 86.6% of patients treated in the day treatment center. Escherichia coli was identified in 84.5% of urine cultures; 98.3% of isolates were sensitive to gentamicin. Six blood cultures (10.3%) yielded positive results, 5 of them for E coli. Treatment with intravenously administered antibiotics in the day treatment center lasted a mean of 2.7 days. The mean number of visits, including appointments for voiding cystourethrography, was 2.9 visits. The rate of parental compliance with day treatment center visits was 98.3%. Intravenous access problems were seen in 8.6% of cases. Successful treatment in the day treatment center (defined as attendance at all visits, normalization of temperature within 48 hours, negative control urine and blood culture results, if cultures were performed, and absence of hospitalization from the day treatment center) was obtained for 86.2% of patients with confirmed urinary tract infections. CONCLUSIONS: Ambulatory treatment of infants 30 to 90 days of age with febrile urinary tract infections by using short-term, intravenous antibiotic therapy at a day treatment center is feasible.

Upper gastrointestinal tract bleeding acquired in a pediatric intensive care unit: Prophylaxis trial with cimetidine

Essai controle en double-insu des effets de la cimetidine (n=19) contre placebo (n=21), chez des enfants de 10 jours a 14 ans. La cimetidine accroit le pH du suc gastrique dans les 3 heures apres la 1ere injection intraveineuse mais ne previent pas les saignements macroscopiques gastro-intertinaux (SMGI) chez les sujets a risque. Le type de prophylaxie est conteste et les transfusions sanguines demeurent indiquees chez les sujets a risque

Acquired carnitine abnormalities in critically ill children

AbstractIn order to characterize the role of carnitine during metabolic stress, we prospectively determined carnitine profiles in plasma and urine on admission, days 2, 5, 10 and 15, among 28 critically ill children free of any known conditions associated with secondary carnitine deficiency. More than 25% of plasma and 50% of urinary carnitine measurements were abnormal; 96% (27/28) of patients displayed on at least one occasion an abnormal [<−2 SD or >+2 SD] carnitine value in plasma. Three children had extremely low [<10 μmol/l] free carnitine (FC) levels in plasma. Plasma esterified and FC levels on admission were not related to the risk of mortality [PRISM score], to muscle lysis [CK values], and to the caloric intake. Levels of FC and esterified carnitine in plasma were unrelated to those measured in urine. Conclusion Abnormal plasma and urine carnitine measurements are frequently found in critically ill children; the biological significance of these perturbations remains unclear. Caution must be exercised before concluding that an abnormal carnitine value is indicative of an underlying hereditary metabolic disorder in this population.