Bonnie J. Taylor

Single-institution experience with interhospital extracorporeal membrane oxygenation transport: A descriptive study.

Objective: Patients with refractory cardiopulmonary failure may benefit from extracorporeal membrane oxygenation, but extracorporeal membrane oxygenation is not available in all medical centers. We report our institutions nearly 20-yr experience with interhospital extracorporeal membrane oxygenation transport. Design: Retrospective review. Setting: Quaternary care childrens hospital. Patients: All patients undergoing interhospital extracorporeal membrane oxygenation transport by the Arkansas Childrens Hospital extracorporeal membrane oxygenation team. Interventions: Data (age, weight, diagnosis, extracorporeal membrane oxygenation course, hospital course, mode of transport, and outcome) were obtained and compared with the most recent Extracorporeal Life Support Organization Registry report. Results: Interhospital extracorporeal membrane oxygenation transport was provided to 112 patients from 1990 to 2008. Eight were transferred between outside facilities (TAXI group); 104 were transported to our hospital (RETURN group). Transport was by helicopter (75%), ground (12.5%), and fixed wing (12.5%). No patient died during transport. Indications for extracorporeal membrane oxygenation in RETURN patients were cardiac failure in 46% (48 of 104), neonatal respiratory failure in 34% (35 of 104), and other respiratory failure in 20% (21 of 104). Overall survival from extracorporeal membrane oxygenation for the RETURN group was 71% (74 of 104); overall survival to discharge was 58% (61 of 104). Patients with cardiac failure had a 46% (22 of 48) rate of survival to discharge. Neonates with respiratory failure had an 80% (28 of 35) rate of survival to discharge. Other patients with respiratory failure had a 62% (13 of 21) rate of survival to discharge. None of these survival rates were statistically different from survival rates for in-house extracorporeal membrane oxygenation patients or for survival rates reported in the international Extracorporeal Life Support Organization Registry (p > .1 for all comparisons). Conclusions: Outcomes of patients transported by an experienced extracorporeal membrane oxygenation team to a busy extracorporeal membrane oxygenation center are very comparable to outcomes of nontransported extracorporeal membrane oxygenation patients as reported in the Extracorporeal Life Support Organization registry. As has been previously reported, interhospital extracorporeal membrane oxygenation transport is feasible and can be accomplished safely. Other experienced extracorporeal membrane oxygenation centers may want to consider developing interhospital extracorporeal membrane oxygenation transport capabilities to better serve patients in different geographic regions.

Assessing Postoperative Pain in Neonates: A Multicenter Observational Study

OBJECTIVE. A multicenter observational study was conducted to evaluate the practices of postoperative pain assessment and management in neonates to identify specific targets for improvement in clinical practice. METHODS. Ten participating NICUs collected data for the 72 hours after a surgical operation on 25 consecutive neonates (N = 250), including demographics, principal diagnoses, operative procedure, other painful procedures, pain assessments, interventions (pharmacologic and nonpharmacologic), and adverse events in neonates who underwent minor and major surgery. Descriptive and logistic-regression analyses were performed by using SPSS and Stata. RESULTS. The neonates studied had a birth weight of 2.4 ± 1.0 kg (mean ± SD) and gestational age of 36 ± 4.3 weeks; 57% were male, and length of hospital stay was 23.5 ± 30.0 days. Participating hospitals used 7 different numeric pain scales, with nursing pain assessments documented for 88% (n = 220) of the patients and physician pain assessments documented for 9% (n = 23) of the patients. Opioids (84% vs 60%) and benzodiazepines (24% vs 11%) were used more commonly after major surgery than minor surgery, and a small proportion (7% major surgery, 12% minor surgery) received no analgesia. Logistic-regression analyses showed that physician pain assessment was the only significant predictor of postsurgical analgesic use, whereas major surgery and postnatal age in days did not seem to contribute. Physician pain assessment was documented for 23 patients; 22 of these received postoperative analgesia. CONCLUSIONS. Documentation of postoperative pain assessment and management in neonates was extremely variable among the participating hospitals. Pain assessment by physicians must be emphasized, in addition to developing evidence-based guidelines for postoperative care and educating professional staff to improve postoperative pain control in neonates.

Influence of repeated upper airway obstruction on the arousal and cardiopulmonary response to upper airway obstruction in lambs.

ABSTRACT: Experiments were done on five Iambs to determine if repeated obstruction of the upper airway influences the arousal and cardiopulmonary response to upper airway obstruction. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electrooculogram, nuchal and diaphragm electromyograms, and measurements of arterial blood pressure and arterial hemoglobin oxygen saturation. A tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea. The animals were studied after a 3-day recovery period. During a study, a 5F balloon-tipped catheter was inserted into the tracheostomy tube so that air flow could be obstructed by inflating the balloon. The balloon was inflated each time the animal went to sleep for approximately 100 consecutive epochs (17 to 30 h) and the time to arousal and the arterial hemoglobin oxygen saturation at arousal were recorded. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred from both sleep states during upper airway obstruction but was delayed in active sleep compared to quiet sleep. The time to arousal and the decrease in arterial hemoglobin oxygen saturation were significantly increased with repeated upper airway obstruction only during active sleep. Inasmuch as it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death, studies to investigate the mechanisms of the state-specific changes in the arousal response to upper airway obstruction are warranted.

Influence of carotid denervation on the arousal and cardiopulmonary responses to upper airway obstruction in lambs.

ABSTRACT: Experiments were done on five lambs to determine if carotid denervation influences the arousal and cardiopulmonary responses to upper airway obstruction during sleep. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms. and measurements of arterial blood pressure and arterial Hb oxygen saturation. A tracheotomy was done and a fenestrated tracheotomy tube placed in the trachea. During the study, a 5 F balloon-tipped catheter was inserted into the tracheotomy tube so that air flow could be obstructed by inflating the balloon. No sooner than 3 d after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing room air and during experimental periods of upper airway obstruction. Carotid denervation significantly affected the arousal response to upper airway obstraction. Arousal occurred during 14 of 14 epochs in quiet sleep and during 12 of 13 epochs in active sleep before the arterial Hb oxygen saturation decreased to 30%. However, the time to arousal was increased and the arterial Hb oxygen saturation at arousal was decreased in carotid-denervated lambs compared with what we have previously observed in carotid-intact lambs. These data provide evidence that the caroid chemoreceptors and/or carotid baroreceptors play a major role in causing arousal from sleep during upper airway obstruction in lambs. Our results may have implications for sudden infant death syndrome, because it is possible that alterations in the arousal response to respiratory stimuli play a role in sudden infant death.

Pharmacokinetics and Pharmacodynamics of Famotidine in Infants

The pharmacokinetics and pharmacodynamics of intravenous famotidine were evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic indication for the prophylactic treatment of stress ulceration. After a 0.5‐mg/kg infusion of famotidine, timed serum (n = 6), urine (24‐hour collection), and repeated measurements of gastric pH were obtained. The mean ± standard deviation maximum plasma concentration (Cmax) was 640.66 ± 250.66 ng/mL, the elimination half‐life (t1/2β) was 10.51 ± 5.43 hours, and the apparent volume of distribution at steady state (Vdss) was 0.82 ± 0.29 L/kg. Plasma clearance (Cl) and renal clearance (ClR) were 0.132 ± 0.061 L/hr/kg and 0.093 ± 0.056 L/hr/kg, respectively. No significant correlations were found between t1/2β, Vdss, Cl, and ClR and age. Six of the nine infants who had intragastric pH monitoring maintained a gastric pH > 4 until the final 24‐hour sampling point. In this study, the t1/2β of famotidine was prolonged and the Vdss, Cl, ClR were reduced compared with corresponding parameters in previously reported studies of children older than one year of age and adults.

Pharmacokinetics and Pharmacodynamics of Ranitidine in Neonates Treated with Extracorporeal Membrane Oxygenation

The pharmacokinetics and pharmacodynamics of ranitidine were studied in 13 term neonates with stable renal and hepatic function who were treated with extracorporeal membrane oxygenation (ECMO). Ranitidine was initially administered as a single 2 mg/kg dose over 10 minutes and intragastric pH was monitored to determine response. Within 90 minutes after administration of ranitidine, intragastric pH for all of the patients whose initial reading was ≤ 4 had increased to > 5. Intragastric pH remained < 4 for a minimum of 15 hours. Mean ± 1 standard deviation elimination half‐life was 6.61 ± 2.75 hours, and 41.5 ± 22.2% of the single dose was eliminated in urine within 24 hours. Total plasma clearance of ranitidine correlated well with estimated glomerular filtration rate. Twenty‐four hours after the initial dose, a continuous infusion of ranitidine (2 mg/kg/24 hr) was started and continued for 72 hours or until ECMO was discontinued. Eleven patients completed 48 hours of continuous infusion and seven completed all 72 hours. Plasma clearance and elimination half‐life were determined from steady‐state plasma ranitidine concentrations 24, 46, and 72 hours after the start of the infusion. There were no significant differences in clearance between these intervals. These data suggest that for term neonates with stable renal and hepatic function, ranitidine does not need to be administered more frequently than every 12 hours. A continuous infusion of 2 mg/kg/24 hours maintained intragastric pH above 4 in more than 90% of our patients, and in our opinion is the preferred method for delivering ranitidine to term neonates undergoing ECMO who require H2 antagonists. Response to therapy should be monitored by repeated measurement of gastric pH and the dose should be adjusted accordingly.

Pulmonary Vascular Response to Aerosolized Cromolyn Sodium and Repeated Epochs of Isocapneic Alveolar Hypoxia in Lambs

ABSTRACT: We investigated the effect of aerosolized cromolyn sodium (CS) on the pulmonary vascular response to isocapneic alveolar hypoxia in chronically instrumented Iambs aged 11–12 days. Each lamb underwent two operations: chest instrumentation for measurements of pulmonary arterial, systemic arterial, and left atrial pressures, and pulmonary blood flow; and a tracheotomy for drug administration. The animals were recovered 3 days before study. Each lamb receiver an aerosol of normal saline (placebo) and CS in paired experiments 24 h apart. In the first set of experiments (n = 8), placebo or CS (30 mg) was given, followed by four 15-min epochs of alveolar hypoxia (8% O2, 5% CO2, 87% N2) each separated by 30 min of alveolar normoxia (21% O2). During hypoxia after both placebo and CS, pulmonary arterial pressure and resistance increased. This response was unchanged with repeated epochs. In the second set of experiments (n = 8), normal saline or CS (30 mg) was administered three times over a 90-min period, followed by one 15-min epoch of hypoxia. Pulmonary arterial pressure and resistance increased during hypoxia after placebo, but did not change after CS. Thus, the single dose of aerosolized CS did not alter the pulmonary vascular response to alveolar hypoxia, whereas the triple dose of CS attenuated the response. Additionally, the pulmonary vascular response to hypoxia alone was not altered by repeated exposures to hypoxia. We conclude that CS interferes with the mechanism(s) responsible for hypoxic pulmonary vasoconstriction in newborn lambs.

Cromolyn Sodium Decreases the Pulmonary Vascular Response to Alveolar Hypoxia in Lambs

ABSTRACT. We investigated the effect of cromolyn sodium, a mast cell stabilizing agent, on the pulmonary vascular response to alveolar hypoxia in six chronically instrumented lambs aged 9 to 11 days. Each lamb was instrumented on day 6 or 7 for measurements of systemic arterial, pulmonary arterial and left atrial pressures, and pulmonary blood flow. The animals were allowed to recover from surgery at least 3 days before they were studied. Each animal was studied twice, once with a cromolyn sodium infusion and once with a normal saline infusion (placebo). These paired experiments were separated by 24 h. Physiologic measurements were made during a 1-min predose control period, after an 8-min drug or placebo infusion, and after a 15-min period of alveolar hypoxia. Cromolyn sodium infusion alone did not affect baseline cardiovascular variables. Alveolar hypoxia following placebo infusion produced an increase in pulmonary arterial pressure and pulmonary vascular resistance; these responses were blocked in the animals given cromolyn sodium prior to induction of hypoxia. These results show that cromolyn sodium blocks the pulmonary vascular response to hypoxia and provide indirect evidence that mast cell degranulation, with subsequent release of vasoactive agents, mediates the pulmonary vascular response to hypoxia in newborn lambs.

Mobile extracorporeal membrane oxygenation

Mobile extracorporeal membrane oxygenation (ECMO) is being offered by select ECMO centers in the United States. Mobile ECMO can be performed for the critically ill patient who is unable to be transported by conventional ambulance transport. This article discusses the logistics and safety considerations associated with mobile ECMO.

383 DISPOSITION OF THEOPHYLLINE AND CAFFEINE IN NEONATAL PIGLETS

A pharmacokinetic (PK) study to evaluate the piglet as a model for theophylline (T) and caffeine (C) disposition was undertaken in 28 animals who received a 10 mg/kg IV bolus injection of C or T, followed by multiple blood sampling over 24 hours. C and T were quantitated from serum by HPLC (CV<3% at 0.1-100 mg/L). Comparison of T and C disposition was performed at 2 (n=6 per group), 4-5 (n=4 per group) and 19-20 (n=4 per group) days of age, and resulted in the following data (mean):With the exception of T clearance (CL) between the 4.25 and 20.25 day groups, and Vdarea for all age groups, there were significant (p<0.05) differences for C and T PK parameters between all age groups. C was not detectable in piglets receiving T; however, T was detected (0.4±0.2 mg/L at 11.5±4.2 hr) in the 4 oldest piglets receiving C. PK parameters for C and T in piglets studied at 2 days of age were similar to those reported in human neonates. In the older animals, they were markedly different than values reported for human neonates of similar age. Furthermore, ability for T biotransformation to C appears deficient in the piglet. These differences from human neonates will require further elucidation for piglets to be effective “models”.