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BACKGROUND: A helium-oxygen gas mixture (heliox) has low gas density and low turbulence and resistance through narrowed airways. The effects of heliox on pulmonary mechanics following severe methacholine-induced bronchospasm were investigated and compared to those of a nitrogen-oxygen gas mixture (nitrox) in an innovative pediatric porcine, independent lung, mechanical ventilation model. RESULTS: All of the lungs showed evidence of severe bronchospasm after methacholine challenge. Prospective definition of 'heliox response' was a 15% or greater improvement in lung function in the lung receiving heliox compared with the matched lung receiving nitrox. Seven out of 10 pigs responded to heliox therapy with respect to resistance and eight out of 10 pigs responded to heliox therapy with respect to compliance and tidal volume (P < 0.03). After crossover from nitrox to heliox, eight out of eight lungs significantly improved with respect to tidal volume, resistance and compliance (P < 0.001). After crossover from heliox to nitrox all eight lungs showed a significant increase in resistance and a significant decrease in tidal volume (P < 0.001). CONCLUSIONS: In a pediatric porcine model of acute, severe methacholine-induced bronchospasm and independent lung mechanical ventilation, administration of heliox improves pulmonary mechanics, gas flow, and ventilation. Administration of heliox should be considered for support of pediatric patients with acute, severe bronchospasm requiring mechanical ventilation through small artificial airways.

Objective: To teach residents to recognize and treat critically ill or injured infants, children, and adolescents in a 1-month, intensivist-designed, second-year resident pediatric intensive care rotation curriculum while maintaining optimal patient care and resident educational satisfaction., Design: Descriptive evaluation of an intensivist-designed, second-year resident pediatric intensive care rotation curriculum from September 1994 to May 1996., Setting: Multispecialty 16-bed pediatric intensive care unit (ICU) staffed by five pediatric critical care physicians in a university-affiliated children's hospital supporting a pediatric residency program., Patients: None., Interventions: None., Measurements and Main Results: Our second-year resident pediatric ICU rotation curriculum consisted of direct patient care, participation in clinical rounds under the supervision of a pediatric critical care attending physician, and a 1-month formal curriculum. A standardized test evaluated resident pediatric critical care knowledge before and after the pediatric ICU rotation. Number and type of resident procedures were documented. Four-point Likert scale questionnaires were used to evaluate resident educational satisfaction and resident performance. Opportunity cost, the graduate medical education return on educational investment, the critical care attending physician's return on resident investment, and the optimal teaching time for number of rotation residents were calculated. Unit demographics were documented. Data analysis included multivariate analysis, t-test, and chi-squared techniques. Significance was defined as p < .05, rotated factor loading > 0.5, and Eigenvalues > or = 1. Kmeans identified clusters. From September 1994 to May 1996, 71 residents, 34 (48%) from pediatric or medicine-pediatric programs and 37 (52%) from emergency medicine residency programs, participated in our second-year pediatric ICU resident educational process. All residents showed improvement between pretest and posttest knowledge scores (p < .05). Seventy percent of the variance in critical care attending physician evaluations of the residents during their pediatric ICU rotation was based on bedside clinical skills (31%), communication skills (20%), and basic knowledge base (19%). Critical care attending physician evaluations of residents placed residents into three clusters: "hands-on," "well-rounded," or "book-heavy" residents. Prerotation test scores, postrotation test scores, and numbers of procedures performed did not correlate with how critical care attending physicians evaluated overall performances of individual residents. Three factors explained 61% of the variances in resident satisfaction with the pediatric ICU rotation: clinical experience (27%), formal didactics (18%), and text availability (16%). Resident educational satisfaction did not appear to depend on access to procedures. Critical care attending physicians spent a minimum of 12.6 hrs/wk involved in resident education. The opportunity cost for using critical care attending physicians to provide 12.6 resident teaching hours per week was calculated as $111,384/yr. Pediatric ICU patient demographics, morbidity, and mortality did not change during the introduction of the resident educational program in the pediatric ICU., Conclusions: During a required pediatric ICU resident rotation, balancing the resident's educational and decision-making autonomy needs and the critical care attending physician's desire to provide consistent bedside care of the critically ill child is an ongoing interactive process that requires substantial personnel, time, and financial commitments. It is possible to maintain patient care in the pediatric ICU and provide residents with a satisfying pediatric ICU experience. Trends in financial reimbursement may limit our present time commitment to the resident pediatric ICU curriculum.

The effects of three anesthetic regimens on an established model of pediatric porcine hypoxic-hypercarbic arrest were examined. Twenty-four preadolescent miniature piglets were paralyzed, mechanically ventilated and anesthetized with one of three regimens: IM + IV pentobarbital (n = 8); IM + IV ketamine (n = 8); or IM ketamine+inhaled isoflurane (n = 8). Asphyxial cardiopulmonary arrest was induced and, after and 8 min cardiac arrest nonintervention interval, a standardized protocol of manual CPR with mechanical ventilation was performed. Outcome variables included incidence of ventricular fibrillation, time to cardiac arrest, endogenous plasma epinephrine levels and arteriovenous epinephrine gradients. IV Ketamine anesthesia produced the highest incidence of ventricular fibrillation (P < 0.01 vs. pentobarbital and isoflurane). Time to asphyxia induced cardiac arrest was greatest for the pentobarbital group (P < 0.05 vs. ketamine and isoflurane). During induction of asphyxial cardiac arrest (low cardiac flow), endogenous venous epinephrine accumulation was highest in the pentobarbital anesthetized group (P < 0.05). After 8 min of untreated cardiac arrest and 1 min of CPR (low flow), arterial epinephrine levels were highest in the ketamine group (P < 0.05). Endogenous epinephrine gradients were venous > arterial in all groups at the end of the 8 min cardiac arrest non-intervention interval (no flow). After 1 min of CPR, the gradients had either equalized or reversed to arterial > venous in all groups except for pentobarbital. As designed and expected, return of spontaneous circulation did not occur in any animal. We conclude that, in developing models of porcine asphyxial cardiopulmonary arrest and resuscitation to simulate pediatric human arrest, variations in anesthetic regimen produce significant differences in parameters that are important to consider: time to asphyxia induced cardiac arrest, fibrillation threshold, plasma epinephrine level and arteriovenous epinephrine gradient. Anesthetic effects need to be carefully considered and clearly explained to facilitate the interpretation of studies of interventions in cardiopulmonary arrest and resuscitation.

Objective: To determine the efficacy of transdermal clonidine hydrochloride for prophylaxis of withdrawal syndromes that are common following more than 7 days of deep sedation after single-stage laryngotracheal reconstruction (LTR) surgery., Design: Consecutive case series., Setting: Pediatric intensive care unit at tertiary care referral center, university-affiliated children's hospital., Patients: Ten consecutive patients who had undergone single-stage LTR and received sedation with a combination of narcotics and benzodiazepines., Interventions: A sustained release transdermal clonidine hydrochloride patch (50-100 micrograms/d; mean, 5.8 micrograms/kg per day; range, 4.2-8.5 micrograms/kg per day) was applied to 8 consecutive patients before discontinuation of sedative infusions and elective extubation. Physicians continued to treat patients for withdrawal symptoms, if seen, at their discretion., Main Outcome Measures: Seventeen characteristic narcotic and sedative withdrawal symptoms recorded at baseline and serially for at least 48 hours following discontinuation of deep sedation., Results: No severe symptoms of narcotic or sedative withdrawal (seizure, choreoathetosis, tremors, or dehydration) were seen in any patient during treatment with clonidine. Not more than 2 minor withdrawal symptoms (lethargy and respiratory rate > 40 breaths/min) occurred simultaneously during treatment with clonidine in any patient. Two of 8 patients had clonidine patches removed prematurely. Both patients experienced withdrawal symptoms within hours, and these symptoms subsided in the 1 patient whose clonidine patch was reinstituted. No significant sustained side effects, bradycardia, or dysrhythmia necessitated discontinuation of clonidine therapy, and no rebound withdrawal was seen with routine discontinuation of clonidine after 7 days of therapy., Conclusions: Transdermal clonidine prophylaxis may be a safe and efficacious adjunct to prevent withdrawal symptoms in pediatric patients who have undergone single-stage LTR. Use of a validated withdrawal symptom scoring tool is indicated for patients undergoing single-stage LTR and requiring prolonged, deep sedation in the pediatric intensive care unit.

Objective: To compare timed inspiratory-cycle endotracheal (ET) instillation of epinephrine (EPI) with instillation during apnea during CPR., Methods: Prospective randomized laboratory comparison of two ET-EPI instillation techniques in 24 preadolescent anesthetized and paralyzed Yucatan swine (mean weight 10.3 +/- 1.5 kg) with apnea-induced hypoxic and hypercarbic cardiopulmonary arrest. After 8 minutes of cardiopulmonary arrest and 1 minute of CPR, 500 microgram(s) (50 +/- 7 microgram(s)/kg) of radiolabeled ET EPI was either administered timed to a ventilator inpspiratory cycle (IN, n = 15) or injected during apnea (DA, n = 9) using a monitoring lumen built into the sidewall of the ET tube. Injection technique was carefully controlled regarding ET-tube position, dilution, flush, and pressure-limited mechanical ventilations. CPR was resumed and continued for 5 minutes. If resuscitation occurred, monitoring was continued for one hour. Outcome variables included pulmonary EPI distribution pattern (DIST), plasma exogenous and total EPI levels, successful resuscitation, and hemodynamic response., Results: Bilateral DIST occurred in 58% of the pigs, with significantly more bilateral DISTs for IN versus DA pigs (p = 0.01). Plasma radiolabeled exogenous EPI counts were significantly greater for IN versus DA pigs (p = 0.03). Total plasma EPI levels rose significantly above baseline over time within each group, but showed no difference between the IN and DA groups at any time point. Successful resuscitation occurred in 21% of the pigs, with no difference between IN and DA pigs (p = 0.38)., Conclusion: When other aspects of ET EPI instillation are optimized and controlled during porcine hypoxic-hypercarbic arrest, timed inspiratory-cycle installation of ET EPI (50 microgram(s)/kg) results in an improved bilateral DIST and greater exogenous EPI absorption. However, in this severe pediatric asphyxial arrest model using a 50-microgram(s)/kg dose, inspiratory-cycle instillation does not improve the resuscitation rate or hemodynamic response over currently recommended instillation during apnea.

Objective: To compare three endotracheal epinephrine instillation techniques in a pediatric porcine hypoxic-hypercarbic cardiopulmonary arrest model., Design: Prospective, randomized, laboratory comparison of three instillation techniques., Setting: Large animal research facility at a children's hospital., Subjects: Thirty-six preadolescent anesthetized and paralyzed Yucatan swine (mean weight 10.0 +/- 1.9 kg) with apnea-induced hypoxic and hypercarbic cardiopulmonary arrest., Interventions: After 8 mins of cardiopulmonary arrest and 1 min of cardiopulmonary resuscitation (CPR), 500 micrograms (51 +/- 9 micrograms/kg) of radiolabeled endotracheal epinephrine was administered by direct injection (n = 17), injection via feeding catheter (n = 10), or via monitoring lumen built into the sidewall of the endotracheal tube (n = 9). CPR was resumed and continued for 5 mins. If resuscitation occurred, monitoring was continued for 1 hr. Outcome variables included successful resuscitation, pulmonary distribution, heart rate, mean arterial pressure, plasma radiolabeled epinephrine counts, and total plasma epinephrine concentrations. Analysis by Fisher's exact test, one-way analysis of variance and Pearson's phi coefficient was performed., Measurements and Main Results: Successful resuscitation occurred in 31% of all pigs with no difference between groups (p = .69). Bilateral distribution occurred in 39% with no difference between groups (p = .25). No correlation was noted between successful resuscitation and distribution (p = .65). HR, mean arterial pressure, plasma radiolabeled epinephrine counts, and total plasma epinephrine concentrations showed significant changes over time within groups, but no difference between groups at any time point. Adherence of the epinephrine dose to the endotracheal tube was < or = 1.5% in all cases., Conclusions: Instillation of 50 micrograms/kg of endotracheal epinephrine by three different techniques during pediatric porcine asphyxial arrest does not affect resuscitation rate, pulmonary distribution, hemodynamic response, or plasma exogenous and total epinephrine concentrations. No correlation was found between successful resuscitation and bilateral distribution. Therefore, currently recommended cumbersome endotracheal epinephrine instillation techniques may offer no resuscitation advantage over commonly used direct injection in this setting.

Measurements of the saturation of arterial blood with oxygen (SaO2) were compared in 24 children during sickle cell crises. Simultaneous pulse oximetry (Nellcor N-100 pulse oximeter) and arterial blood analysis showed that SaO2 measured by pulse oximetry overestimated cooximeter-measured SaO2 (mean bias, 6.9%; p < 0.001). The blood gas machine-calculated SaO2 also overestimated cooximeter-measured SaO2 (p < 0.001). The bias increased with increasing age (p = 0.002) and carboxyhemoglobin level (p = 0.005) but was not related to methemoglobin, total hemoglobin, percentage of hemoglobin S, or percentage of hemoglobin F.

Recent evidence suggests that pentoxifylline (PTX) may be useful in the treatment of sepsis. We examined effects of PTX in a conscious swine model of sepsis. Yucatan minipigs (20-30 kg) were anesthetized and instrumented with catheters in the vena cava, aortic arch, pulmonary artery (Swan-Ganz thermodilution catheter), and peritoneum. Twenty-four hours after surgery, sepsis was induced by intraperitoneal (ip) injection of Escherichia coli bacteria (2 x 10(10) cfu/kg). Nonseptic pigs received intraperitoneal saline (5 ml/kg). PTX treatment (3 mg/kg/hr, iv; 1 mg/ml in 0.9% saline) and maintenance fluid (5 ml/kg/hr, iv) were started with bacterial infusion. An additional 60 cc/kg 0.9% saline bolus was administered iv at 1 hr. Pigs were monitored before and 1, 2, 5, and 24 hr after bacterial injection. Intraperitoneal injection of bacteria led to significant reductions in blood pressure and cardiac output and elevations in pulmonary wedge pressure and pulmonary vascular resistance. These effects were attenuated by PTX treatment. All septic animals demonstrated elevated creatinine, blood urea nitrogen, circulating endotoxin (LPS), and tumor necrosis factor concentrations, reductions in white blood cell and platelet counts, and peritonitis. None of these responses was altered by PTX treatment. We conclude that PTX may prove to be a useful therapeutic tool in the early treatment of septic shock but is limited in the scope of its effects.

Depending on the dose and dosing, pentoxifylline (PTX) treatment can improve or worsen survival from lipopolysaccharide (LPS) shock in rats. Intraperitoneal (i.p.) PTX, 20 mg/kg, administered once 15 min after intravenous (i.v.) LPS (17 mg/kg), significantly improved survival in unanesthetized LPS-shocked rats. Multiple 20 mg/kg PTX injections (five total, spaced at 45 min intervals starting 15 min after LPS) significantly worsened survival. A lower dose, 12 mg/kg, given as a single or multiple injections, did not alter survival. We tested the ex vivo contractile response to norepinephrine (NE) of aortic rings isolated 3.75 hr after i.v. injection of PBS or LPS. Both untreated LPS-shocked and multiple 12 mg/kg PTX treated normal rats (i.v. PBS) had significantly diminished maximum contractility. The ex vivo vascular hypocontractility found in untreated LPS-shocked rats was not aggravated nor ameliorated by multiple 12 mg/kg PTX injections. The ex vivo effects on contractility of multiple 20 mg/kg PTX treatment of LPS shock could not be studied because survival times were shorter than 3.5 hr. In using PTX to treat LPS shock, potentially harmful vasodilation must be considered.

Seven Yucatan minipigs with chronic, severe intraperitoneal sepsis were given amrinone i.v. (loading dose of 0.75 mg/kg, followed by continuous infusion of 10, 20, 40, and 80 micrograms/kg/min) during the hyperdynamic phase of sepsis. Hemodynamic variables and oxygen utilization, delivery, and extraction were recorded throughout the study. Pulmonary capillary wedge pressure was kept constant to ensure a fixed ventricular filling pressure. Intravenous amrinone modestly augmented cardiac index without altering heart rate. Mean systemic and pulmonary arterial pressures decreased. Systemic and pulmonary vascular resistance fell significantly (P less than 0.05). Amrinone did not significantly alter oxygen utilization or oxygen extraction, although oxygen delivery increased (P less than .05). During the hyperdynamic phase of sepsis in this animal model, amrinone elicits vasodilatation with a modest improvement in stroke volume index. Consequently, cardiac output and oxygen delivery increased modestly. Because of its vasodilating properties and small salutary effects, amrinone is not an optimal first-line medication for hemodynamic stabilization during hyperdynamic sepsis.