Peter N. Cox

Outcome of Out-of-Hospital Cardiac or Respiratory Arrest in Children

BACKGROUND Among adults who have a cardiac arrest outside the hospital, the survival rate is known to be poor. However, less information is available on out-of-hospital cardiac arrest among children. This study was performed to determine the survival rate among children after out-of-hospital cardiac arrest and to identify predictors of survival. METHODS We reviewed the records of 101 children (median age, two years) with apnea or no palpable pulse (or both) who presented to the emergency department at the Hospital for Sick Children in Toronto. The characteristics of the patients and the outcomes of illness were analyzed. We assessed the functional outcome of the survivors using the Pediatric Cerebral and Overall Performance Category scores. RESULTS Overall, there was a return of vital signs in 64 of the 101 patients; 15 survived to discharge from the hospital, and 13 were alive 12 months after discharge. Factors that predicted survival to hospital discharge included a short interval between the arrest and arrival at the hospital, a palpable pulse on presentation, a short duration of resuscitation in the emergency department, and the administration of fewer doses of epinephrine in the emergency department. No patients who required more than two doses of epinephrine or resuscitation for longer than 20 minutes in the emergency department survived to hospital discharge. The survivors who were neurologically normal after arrest had had a respiratory arrest only and were resuscitated within five minutes after arrival in the emergency department. Of the 80 patients who had had a cardiac arrest, only 6 survived to hospital discharge, and all had neurologic sequelae. CONCLUSIONS These results suggest that out-of-hospital cardiac arrest among children has a very poor prognosis, especially when efforts at resuscitation continue for longer than 20 minutes and require more than two doses of epinephrine.

Lung recruitment and lung volume maintenance: a strategy for improving oxygenation and preventing lung injury during both conventional mechanical ventilation and high-frequency oscillation

Objective: To determine whether using a small tidal volume (5 ml/kg) ventilation following sustained inflation with positive end-expiratory pressure (PEEP) set above the critical closing pressure (CCP) allows oxygenation equally well and induces as little lung damage as high-frequency oscillation following sustained inflation with a continuous distending pressure (CDP) slightly above the CCP of the lung.¶Material and methods: Twelve surfactant-depleted adult New Zealand rabbits were ventilated for 4 h after being randomly assigned to one of two groups: group 1, conventional mechanical ventilation, tidal volume 5 ml/kg, sustained inflation followed by PEEP > CCP; group 2, high-frequency oscillation, sustained inflation followed by CDP > CCP.¶Results: In both groups oxygenation improved substantially after sustained inflation (P < 0.05) and remained stable over 4 h of ventilation without any differences between the groups. Histologically, both groups showed only little airway injury to bronchioles, alveolar ducts, and alveolar airspace, with no difference between the two groups. Myleoperoxidase content in homogenized lung tissue, as a marker of leukocyte infiltration, was equivalent in the two groups.¶Conclusions: We conclude that a volume recruitment strategy during small tidal volume ventilation and maintaining lung volumes above lung closing is as protective as that of high-frequency oscillation at similar lung volumes in this model of lung injury

Remote ischaemic preconditioning protects against cardiopulmonary bypass-induced tissue injury: a preclinical study.

Objectives: To test the hypothesis that remote ischaemic preconditioning (rIPC) reduces injury after cardiopulmonary bypass (CPB). Design: Randomised study with an experimental model of CPB (3 h CPB with 2 h of cardioplegic arrest). Twelve 15 kg pigs were randomly assigned to control or rIPC before CPB and followed up for 6 h. Intervention: rIPC was induced by four 5 min cycles of lower limb ischaemia before CPB. Main outcome measures: Troponin I, glial protein S-100B, lactate concentrations, load-independent indices (conductance catheter) of systolic and diastolic function, and pulmonary resistance and compliance were measured before and for 6 h after CPB. Results: Troponin I increased after CPB in both groups but during reperfusion the rIPC group had lower concentrations than controls (mean area under the curve −57.3 (SEM 7.3) v 89.0 (11.6) ng·h/ml, p  =  0.02). Lactate increased after CPB in both groups but during reperfusion the control group had significantly more prolonged hyperlactataemia (p  =  0.04). S-100B did not differ between groups. Indices of ventricular function did not differ. There was a tendency to improved lung compliance (p  =  0.07), and pulmonary resistance changed less in the rIPC than in the control group during reperfusion (p  =  0.02). Subsequently, peak inspiratory pressure was lower (p  =  0.001). Conclusion: rIPC significantly attenuated clinically relevant markers of myocardial and pulmonary injury after CPB. Transient limb ischaemia as an rIPC stimulus has potentially important clinical applications.

Measles Inclusion-Body Encephalitis Caused by the Vaccine Strain of Measles Virus

We report a case of measles inclusion-body encephalitis (MIBE) occurring in an apparently healthy 21-month-old boy 8.5 months after measles-mumps-rubella vaccination. He had no prior evidence of immune deficiency and no history of measles exposure or clinical disease. During hospitalization, a primary immunodeficiency characterized by a profoundly depressed CD8 cell count and dysgammaglobulinemia was demonstrated. A brain biopsy revealed histopathologic features consistent with MIBE, and measles antigens were detected by immunohistochemical staining. Electron microscopy revealed inclusions characteristic of paramyxovirus nucleocapsids within neurons, oligodendroglia, and astrocytes. The presence of measles virus in the brain tissue was confirmed by reverse transcription polymerase chain reaction. The nucleotide sequence in the nucleoprotein and fusion gene regions was identical to that of the Moraten and Schwarz vaccine strains; the fusion gene differed from known genotype A wild-type viruses.

Renal replacement therapy after repair of congenital heart disease in children: A comparison of hemofiltration and peritoneal dialysis

The development of renal failure necessitating peritoneal dialysis after cardiac operations is associated with a reported mortality greater than 50%. Improved fluid removal and nutritional support have been reported with the use of continuous arteriovenous hemofiltration and continuous venovenous hemofiltration techniques. We have compared our experience with all three techniques in managing children who required renal replacement therapy after cardiac operations in terms of efficacy (fluid removal, calorie intake, and clearance of urea and creatinine), complications, and outcome. Over a 5-year period renal replacement therapy was initiated in 42 children, and in 34 of them it was successfully established for more than a 24-hour period: 17 were managed with peritoneal dialysis, 8 with continuous arteriovenous hemofiltration, and 9 with continuous venovenous hemofiltration. A net negative fluid balance was achieved in only 6 (35%) patients treated with peritoneal dialysis compared with 50% of those treated with continuous venovenous hemofiltration and 89% of those treated with continuous venovenous hemofiltration. In terms of nutritional support, calorie intake increased by 43% after peritoneal dialysis was started compared with 515% and 409% in the arteriovenous and venovenous hemofiltration groups, respectively, (p < 0.005). The serum urea levels fell by 36% (p = 0.02) and 39% (p = 0.005) compared with pre-therapy levels with arteriovenous and venovenous hemofiltration, respectively, and the creatinine content was reduced by 19% and 33% (p = 0.003). Neither parameter was reduced in the peritoneal dialysis group. We conclude that the use of hemofiltration as a renal replacement therapy after surgical correction of congenital heart disease offers significant advantages over the more traditional approach of peritoneal dialysis. In addition, we suggest that a more aggressive approach to the management of fluid overload and nutritional depletion with hemofiltration may result in a decrease in the very high mortality seen in renal failure after cardiac operations.

Fellowship training, workload, fatigue and physical stress: a prospective observational study

Background: Fatigue in physician trainees may compromise patient safety and the well-being of the trainees and limit the educational opportunities provided by training programs. Anecdotal evidence suggests that the on-call workload and physical demands experienced by trainees are significant despite duty-hour regulation and support from nursing staff, other trainees and staff physicians. Methods: We measured the workload and the level of fatigue and physical stress of 11 senior fellows during 35 shifts in the critical care unit at the Hospital for Sick Children in Toronto. We determined number of rostered hours, number of admissions and discharges, number and type of procedures, nurse:patient ratios and related measures of workload. Fellows self-reported the number of pages they received and the amount of time they slept. We estimated physical stress by using a commercially available pedometer to measure the distance walked, by using ambulatory electrocardiographic monitoring to determine arrhythmias and by determining urine specific gravity and ketone levels to estimate hydration. Results: The number of rostered hours were within current Ontario guidelines. The mean shift duration was 25.5 hours (range 24–27 hours). The fellows worked on average 69 hours (range 55–106) per week. On average during a shift, the fellows received 41 pages, were on non-sleeping breaks for 1.2 hours, slept 1.9 hours and walked 6.3 km. Ketonuria was found in participants in 7 (21%) of the 33 shifts during which it was measured. Arrhythmia (1 atrial, 1 ventricular) or heart rate abnormalities occurred in all 6 participants. These fellows were the most senior in-house physician for a mean of 9.4 hours per shift and were responsible for performing invasive procedures in two-thirds of their shifts. Interpretation: Established Canadian and proposed American guidelines expose trainees to significant on-call workload, physical stress and sleep deprivation.

Persistent pulmonary hypertension of the newborn due to alveolar capillary dysplasia.

Three unrelated female term infants died when less than 1 month old from intractable pulmonary hypertension associated with deficient capillaries in airspace walls, anomalous small pulmonary veins in bronchiolar-arterial rays, and medial thickening in small pulmonary arteries together with peripheral muscularization. This complex vascular abnormality in the lungs has been termed alveolar capillary dysplasia and/or misalignment of lung vessels in seven previously reported cases. Each infant also showed abnormally immature parenchymal development in the lungs, as was noted in four of the seven prior cases. One had phocomelia; four of the seven prior cases had a variety of congenital anomalies. The primary pulmonary vascular anomaly is likely to be a failure of fetal lung vascularization dating from the second trimester and to be due to action of an unknown teratogen. Centroacinar veins may represent bronchial veins that do not normally develop beyond the ends of cartilaginous bronchi. Pulmonary arterial occlusive changes are interpreted as reactive to obstruction at the level of pulmonary arterioles.

Aerosol delivery of an enhanced helper-dependent adenovirus formulation to rabbit lung using an intratracheal catheter

Poor transduction of the ciliated airway epithelium and inefficient airway delivery of viral vectors are common difficulties encountered in lung gene therapy trials with large animals and humans.

Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

Chitosan is a natural, cationic polysaccharide derived from fully or partially deacetylated chitin. Chitosan is capable of inducing large phospholipid aggregates, closely resembling the function of nonionic polymers tested previously as additives to therapeutic lung surfactants. The effects of chitosan on improving the surface activity of a dilute lung surfactant preparation, bovine lipid extract surfactant (BLES), and on resisting albumin-induced inactivation were studied using a constrained sessile drop (CSD) method. Also studied in parallel were the effects of polyethylene glycol (PEG, 10 kD) and hyaluronan (HA, 1240 kD). Both adsorption and dynamic cycling studies showed that chitosan is able to significantly enhance the surface activity of 0.5 mg/mL BLES and to resist albumin-induced inactivation at an extremely low concentration of 0.05 mg/mL, 1000 times smaller than the usual concentration of PEG and 20 times smaller than HA. Optical microscopy found that chitosan induced large surfactant aggregates even in the presence of albumin. Cytotoxicity tests confirmed that chitosan has no deleterious effect on the viability of lung epithelial cells. The experimental results suggest that chitosan may be a more effective polymeric additive to lung surfactant than the other polymers tested so far.

Nosocomial infection following cardiovascular surgery: Comparison of two periods, 1987 vs. 1992

OBJECTIVE To evaluate whether changes have occurred at our center in the rate of nosocomial infections and in the infectious organisms consequent to changes in policy and procedure as of 1987. SETTING Multidisciplinary pediatric intensive care unit (PICU) in a major tertiary care center. DESIGN Prospective comparative study. PATIENTS Four-hundred and fifty-five consecutive patients who underwent cardiac surgery within a 10-month period. INTERVENTIONS Changes related to antibiotic use and invasive device management were introduced after the 1987 survey. To determine the effect of these changes, all patients undergoing cardiac surgery between July 1991 and April 1992 were followed daily from PICU admission to 2 months after hospital discharge for signs of infection. Each infectious episode was reviewed by the nosocomial infection control committee. A weighted scoring system was used to determine risk. MEASUREMENTS AND MAIN RESULTS In the 1987 study, 40 of 310 patients had 78 infections for a nosocomial infection ratio (NIR) of 25.2. Of the 455 patients surveyed in 1992, 72 had 91 episodes of infection. The nosocomially infected patient rate was 15.8 and the NIR was 20. The frequency of wound infection decreased from 7% in 1987 to 4.3% in this study, and no episode of mediastinitis was observed. In the bacteriological spectrum, the absence of candidal infection was significant, and there was a decrease in the proportional frequency of pseudomonas infection from 21% to 15%. CONCLUSION The comparison between the two time periods demonstrates that an aggressive approach to managing intravascular catheters and urinary catheters and limiting the use of antibiotics probably affects the spectrum of nosocomial infections.