Avoiding Furosemide Ototoxicity Associated With Single-Ventricle Repair in Young Infants.

OBJECTIVE: To reduce bilateral delayed-onset progressive sensory permanent hearing loss using a systems-wide quality improvement project with adherence to best practice for the administration of furosemide. DESIGN: Prospective cohort study with regular audiologic follow-up assessment of survivors both before and after a 2007-2008 quality improvement practice change. SETTING: The referral center in Western Canada for complex cardiac surgery, with comprehensive multidisciplinary follow-up by the Complex Pediatric Therapies Follow-up Program. PATIENTS: All consecutive patients having single-ventricle palliative cardiac surgery at age 6 weeks old or younger. INTERVENTIONS: A 2007-2008 quality improvement practice change consisted of a Parenteral Drug Monograph revision indicating slow IV administration of furosemide, an educational program, and an evaluation. MEASUREMENTS AND MAIN RESULTS: The outcome measure was the prevalence of permanent hearing loss by 4 years old. Firth multiple logistic regression compared pre (1996-2008) to post (2008-2012) practice change occurrence of permanent hearing loss, adjusting for confounding variables, including all hospital days, extracorporeal membrane oxygenation, cardiopulmonary bypass time, age at first surgery, dialysis, and sepsis. From 1996 to 2012, 259 infants had single-ventricle palliative surgery at age 6 weeks old or younger, with 173 (64%) surviving to age 4 years. Of survivors, 106 (61%) were male, age at surgery was 11.6 days (9.0 d), and total hospitalization days by age 4 years were 64 (42); 18 (10%) had cardiopulmonary resuscitation and 38 (22%) had sepsis at any time. All 173 (100%) had 4-year follow-up. Pre- to postpractice change permanent hearing loss dropped from 17/100 (17%) to 0/73 (0%) of survivors. On Firth multiple logistic regression, the only variable statistically associated with permanent hearing loss was the pre- to postpractice change time period (odds ratio, 0.03; 95% CI, 0-0.35; p = 0.001). CONCLUSIONS: A practice change to ensure slow IV administration of furosemide eliminated permanent hearing loss. Centers caring for critically ill infants, particularly those with single-ventricle anatomy or hypoxia, should review their drug administration guidelines and adhere to best practice for administration of IV furosemide.

Chloral hydrate enteral infusion for sedation in ventilated children: the CHOSEN pilot study.

BACKGROUND: We aimed to test a novel method of delivery of chloral hydrate (CH) sedation in ventilated critically ill young children. METHODS: Children < 12 years old, within 72 hours of admission, who were ventilated, receiving enteral tube-feeds, with intermittent CH ordered were enrolled after signed consent. Patients received a CH loading-dose of 10 mg/kg enterally, then a syringe-pump enteral infusion at 5 mg/kg/hour, increasing to a maximum of 9 mg/kg/hour. Cases were compared to historical controls matched for age group and Pediatric Risk of Mortality score (PRISM) category, using Fisher's exact test and the t test. The primary outcome was feasibility, defined as the use of an enteral CH continuous infusion without discontinuation attributable to a pre-specified potential harm. RESULTS: There were 21 patients enrolled, at age 11.4 (12.1) months, with bronchiolitis in 10 (48%), a mean Pediatric Logistic Organ Dysfunction (PELOD) score of 6.2 (5.2), and having received enteral CH continuous infusion for 4.5 (2.2) days. Infusion of CH was feasible in 20/21 (95%; 95% CI 76-99%) patients, with one (5%) adverse event of duodenal ulcer perforation on day 3 in a patient with croup receiving regular ibuprofen and dexamethasone. The CH infusion dose (mg/kg/h) on day 2 (n = 20) was 8.9 (IQR 5.9, 9), and on day 4 (n = 11) was 8.8 (IQR 7, 9). Days to titration of adequate sedation (defined as ≤ 3 PRN doses/shift) was 1 (IQR 0.5, 2.5), and hours to awakening for extubation was 5 (IQR 2, 9). Cases (versus controls) had less positive fluid balance at 48 h (-2 (45) vs. 26 (46) ml/kg, p = 0.051), and a decrease in number of PRN sedation doses from 12 h pre to 12 hours post starting CH (4.7 (3.3) to 2.6 (2.8), p = 0.009 versus 2.9 (3.9) to 3.4 (5), p = 0.74). There were no statistically significant differences between cases and controls in inotrope scores, signs or treatment of withdrawal, or PICU days. CONCLUSIONS: Delivering CH by continuous enteral infusion is feasible, effective, and may be associated with less positive fluid balance. Whether there is a risk of duodenal perforation requires further study.

Survey of Sedation and Analgesia Practice Among Canadian Pediatric Critical Care Physicians.

BACKGROUND: Despite the fact that almost all critically ill children experience some degree of pain or anxiety, there is a lack of high-quality evidence to inform preferred approaches to sedation, analgesia, and comfort measures in this environment. We conducted this survey to better understand current comfort and sedation practices among Canadian pediatric intensivists. METHODS: The survey was conducted after a literature review and initial focus groups. The survey was then pretested and validated. The final survey was distributed by email to 134 intensivists from 17 PICUs across Canada using the Research Electronic Data Capture system. RESULTS: The response rate was 73% (98/134). The most commonly used sedation scores are Face, Legs, Activity, Cry, and Consolability (42%) and COMFORT (41%). Withdrawal scores are commonly used (65%). In contrast, delirium scores are used by only 16% of the respondents. Only 36% of respondents have routinely used sedation protocols. The majority (66%) do not use noise reduction methods, whereas only 23% of respondents have a protocol to promote day/night cycles. Comfort measures including music, swaddling, soother, television, and sucrose solutions are frequently used. The drugs most commonly used to provide analgesia are morphine and acetaminophen. Midazolam and chloral hydrate were the most frequent sedatives. CONCLUSION: Our survey demonstrates great variation in practice in the management of pain and anxiety in Canadian PICUs. Standardized strategies for sedation, delirium and withdrawal, and sleep promotion are lacking. There is a need for research in this field and the development of evidence-based, pediatric sedation and analgesia guidelines.

Empiric acyclovir for neonatal herpes simplex virus infection.

BACKGROUND: Because neonatal herpes simplex virus (NHSV) infection is difficult to diagnose, there has been a move towards using more empiric acyclovir (ACV). OBJECTIVE: The purpose of this study was to review the use of ACV to optimize future management of NHSV. METHODS: Charts were reviewed for infants started on intravenous ACV up to day 43 of life--January 2001 through February 2007--at five hospitals in Edmonton and Calgary. RESULTS: ACV was started for possible (N = 115) or proven (N = 3) herpes simplex virus (HSV) infection. Six of the infants with possible HSV infection later had proven HSV infection. Seizures (34%), hemodynamic instability (29%) and skin lesions (24%) were the most common indications for ACV. Among the 118 infants, 106 (90%) had cerebrospinal fluid obtained and 82 (69%) had at least one surface swab for HSV but 4 (3%) had no specimens submitted for HSV detection. ACV was continued for 3.9 ± 3.5 days in the infants with no proven HSV disease. Possible nephrotoxicity from ACV was recorded in 3 of these 109 infants and in none of the infants with proven HSV disease. CONCLUSIONS: Clinicians in Alberta primarily consider the diagnosis of NHSV infection when confronted with a neonate with seizures, hemodynamic instability or suspicious skin lesions, but need to consider the diagnosis more often if all cases are to be treated at first presentation. They often perform incomplete investigations to rule out NHSV infection. Adverse events from ACV appear to be uncommon when the drug is used for suspected NHSV disease.

Bilateral sensory permanent hearing loss after palliative hypoplastic left heart syndrome operation.

BACKGROUND: Bilateral sensory permanent hearing loss (PHL) has been reported after neonatal respiratory failure but has rarely been noted in survivors after cardiac operations. We report the prevalence and severity of PHL after Norwood right ventricular-pulmonary artery shunt for hypoplastic left heart syndrome (HLHS), document progressive loss, and explore markers of acute illness and ototoxic medications for PHL. METHODS: This interprovincial longitudinal outcome study after neonatal complex cardiac operations at Stollery Children's Hospital, Edmonton, Alberta, Canada, 2002 to 2007, completed repeated diagnostic audiologic assessments for all survivors by registered pediatric-experienced audiologists. Demographic, surgical, and perisurgical variables, including ototoxic medications, were collected. The association of potentially predictive variables with PHL and its severity were determined by univariate analysis and multiple logistic and linear regression analysis. RESULTS: At an age older than 3.5 years, progressive PHL was present in 12 of 42 survivors (28.6%, 95% confidence interval, 16.2% to 44.8%; mortality, 20.9%). Overall lowest partial pressure of arterial oxygen (odds ratio, 1.315; 95% confidence interval, 1.051 to 1.506), and cumulative dose of furosemide given as bolus (odds ratio, 1.062; 95% confidence interval, 1.018 to 1.109) combined to predict PHL and gave 39% of the variance of PHL severity. Antibiotics and neuromuscular blockers were not associated with PHL. CONCLUSIONS: Monitoring outcomes of neonates after HLHS surgery revealed unexpected PHL associated with hypoxia and bolus administration of furosemide. As survival improves, close follow-up is necessary to identify outcomes and seek modifiable predictive variables. Changes in the mode of furosemide administration may prevent this complication.

Stability of heparin and physical compatibility of heparin/antibiotic solutions in concentrations appropriate for antibiotic lock therapy.

OBJECTIVES: The purpose of this study was to determine the biological stability of heparin and to test for physical compatibility in heparin/antibiotic solutions in concentrations suitable for antibiotic lock therapy. METHODS: Solutions were prepared with heparin 5000 U/mL or heparin 10 U/mL and cefazolin 10 mg/mL, ampicillin 10 mg/mL, or piperacillin 40 mg/mL. Solutions of vancomycin 2.5 mg/mL with heparin 5000 U/mL and vancomycin 2 mg/mL with heparin 10 U/mL were also prepared. The ability of each solution to elevate the activated partial thromboplastin time (APTT) of pooled normal plasma and the physical compatibility of the solutions were assessed for 14 days. RESULTS: The APTT levels never varied by more than 16.4% from baseline. Physical incompatibility never occurred before day 14 in any of the solutions. CONCLUSIONS: Mixing of antibiotics in the concentrations chosen for the study had no clinically significant effect on biological heparin activity, and all solutions were physically compatible for at least 14 days.