Bala R Totapally

Outcome of cardiopulmonary resuscitation in a pediatric cardiac intensive care unit.

ObjectiveTo determine the eventual outcome of children with heart disease who had cardiopulmonary resuscitation (CPR) in a specialized pediatric cardiac intensive care unit (CICU), and to define the influence of any prearrest variables on the outcome. DesignA retrospective review of patients’ medical records. SettingA pediatric CICU of a tertiary pediatric teaching hospital. Patients and MethodsPatients were all children who presented with cardiopulmonary arrest and who were administered CPR in the pediatric CICU between June 1995 and June 1997. Prearrest variables such as age, diagnosis, prior cardiac surgery, and inotropic support with epinephrine, as well as cause of arrest, were evaluated. Measurements and Main ResultsThirty-two patients, ranging in age from 1 day to 21 yrs (median, 1 month), satisfied criteria for inclusion in the study group. These 32 patients had a total of 38 episodes of cardiopulmonary arrest. Twenty-five of these patients (78%) had cardiac surgery before arrest. Inotropic support with continuous infusion of epinephrine was being administered at the time of arrest in 18 of 38 (47%) arrests. These prearrest variables did not influence outcome of CPR.Of the 38 episodes of CPR, 24 episodes (63%) were successful, with 20 episodes resulting in return of spontaneous circulation and four patients being successfully placed on mechanical cardiopulmonary support. Fourteen children, including all four patients who were rescued with mechanical cardiopulmonary support, survived to discharge. At 6-month follow-up, 11 patients were still alive, with three having neurologic impairment. ConclusionsAfter cardiopulmonary resuscitation in this pediatric CICU, the rate of success was 63% and the rate of survival was 42%. Prior cardiac surgery and use of epinephrine before arrest did not influence the outcome of CPR. The availability of effective mechanical cardiopulmonary support can improve the outcome of CPR.

Acute hypercapnia increases the oxygen-carrying capacity of the blood in ventilated dogs

OBJECTIVE To test the hypothesis that PaCO2 levels generated during permissive hypercapnia may enhance arterial oxygenation, when ventilation is maintained. DESIGN Prospective study. SETTING Research laboratory in a hospital. SUBJECTS One group of eight mongrel dogs (four male; four female). INTERVENTIONS The dogs were anesthetized (30 mg/kg iv pentobarbital), intubated, and cannulated in one femoral artery and vein. While paralyzed with 0.1 mg/kg/hr iv vecouronium bromide, all subjects were ventilated with room air. Anesthesia was maintained, using 2 to 3 mg/kg/hr iv pentobarbital. Arterial hypercapnia at the levels generated during permissive hypercapnia was produced by stepwise increases in the dry, inspired Pco2 (PiCO2) (0, 30, 45, 60 and 75 torr [0, 4, 6, 8, and 10 kPa]; 15 mins each). MEASUREMENTS AND MAIN RESULTS Blood gas profiles were determined at each level of hypercapnia. The minute volume was maintained at the baseline level during all exposures. Arterial hypercapnia produced gradual and significant increases in the hemoglobin concentration. These increases were approximately 6%, 7%, 11%, and 14% at PiCO2 of 30, 45, 60, and 75 torr (4, 6, 8, and 10 kPa), respectively (p < .05; repeated analysis of variance followed by Dunnett multiple comparisons test). In parallel, the oxygen content increased by approximately 6%, 7%, 11%, and 13%, respectively. During hypercapnic trials, the PaO2 remained at the normal range, whereas the dry, inspired PO2 (PiO2) was reduced from 150 to 138 torr (20 to 18.4 kPa). The average PaO2 at the highest investigated level of arterial hypercapnia was at a normal range. The hemoglobin concentration and oxygen content returned to baseline values 30 mins after hypercapnic trials. The PaCO2 and pH became normalized 15 mins after hypercapnic trials. Indirect evidence for a similar response to hypercapnia in humans is presented. CONCLUSIONS Permissive hypercapnia due to inhaled CO2 increases oxygen-carrying capacity in dogs. The PaO2 remains at normal range even at a PiCO2 of 75 torr (10 kPa). The benefits of these effects during permissive hypercapnia, due to controlled hypoventilation, warrants investigation.

Oxygen-carrying capacity during 10 hours of hypercapnia in ventilated dogs

Objective To test if a relatively long-term exogenous hypercapnia, equivalent to those maintained during permissive hypercapnia, can persistently increase oxygen-carrying capacity in ventilated dogs. Design Prospective study. Setting Research laboratory in a hospital. Subjects Six mongrel dogs (3 males; 3 females). Interventions The dogs were anesthetized (30 mg/kg pentobarbital, iv), intubated, and cannulated in one femoral artery, one femoral vein, and the right jugular vein. The mean arterial blood pressure, heart rate, and mean pulmonary artery pressure were continuously recorded. Anesthesia, fluid balance, and normothermia were maintained. Arterial hypercapnia was generated by the addition of 60 torr dry CO2 (8 kPa) to the inspired air for 10 hrs, continuously. All subjects were paralyzed (vecuronium bromide) and ventilated with room air, while the ventilator settings were kept constant. Measurements and Main Results Arterial and venous gas exchange profiles, hemoglobin concentration, oxygen saturation, oxygen content, cardiac output, and oxygen consumption were determined, before, during, and after 10 hrs of hypercapnia, periodically. Both hemoglobin concentration and oxygen content were gradually increased during hypercapnia and reached significant levels at 8 and 10 hrs of hypercapnia, respectively. These increases continued up to 2 hrs after termination of hypercapnia. The Pao2/Fio2, as an index of arterial oxygenation, was significantly increased during the first 3 hrs of hypercapnia and then remained at the normoxic level up to 10 hrs of hypercapnia. No significant changes occurred in the mean arterial blood pressure and oxygen consumption. The heart rate and cardiac output were significantly reduced at 4 and 8 hrs of hypercapnia, respectively. The mean pulmonary artery pressure was increased throughout the hypercapnic trial. Conclusions A relatively long-term exogenous hypercapnia can significantly increase oxygen-carrying capacity in normal ventilated dogs. Whether this effect can occur during permissive hypercapnia because of controlled ventilation in patients warrants investigation.

Experimental critical care in ventilated rats: Effect of hypercapnia on arterial oxygen-carrying capacity

PURPOSE We have previously demonstrated an increased arterial O2-carrying capacity in normal ventilated dogs subjected to both acute and prolonged exogenous hypercapnia. In the present study, we tested if arterial hypercapnia, during controlled ventilation, can increase O2-carrying capacity also in rats. MATERIALS AND METHODS Twenty young male Sprague Dawley rats were anesthetized (60 mg/kg pentobarbital), tracheostomized, intubated, and one femoral vein and artery were cannulated. Anesthesia and paralysis were maintained using 15 mg/kg/h pentobarbital intravenously, and 2 mg/kg/h vecuronium bromide. The fluid balance (5 mL/kg/h saline), normothermia, and minute volume were maintained. The mean arterial blood pressure and heart rate were continuously monitored. Experiments included the following: (1) a control group, ventilated with normoxic air for 150 minutes (n = 5); (2) mild hypercapnia, a group of eight rats ventilated with normoxic air for 30 minutes and then ventilated with a mixture of normoxic air at 60 mm Hg CO2 (8 kPa) for 1 hour; and (3) severe hypercapnia, a group of seven rats were treated exactly as in group II, except a 90 mm Hg (12 kPa) CO2 during hypercapnia. Gas-exchange profile, arterial hemoglobin (Hb) concentration, arterial Hb-oxygen saturation (Hb-O2), and arterial O2 content were periodically determined during normocapnia and 1 hour of hypercapnia. RESULTS Exposures to mild and severe hypercapnia, in rats with maintained ventilation, significantly reduced the arterial O2 content by 20% and 33%, respectively, without significant changes in the arterial Hb concentration (-2%). Severe hypercapnia generated a significant reduction of -14% in the PaO2, but not in PaO2/ FiO2 ratio. CONCLUSION Rats subjected to controlled ventilation and permissive hypercapnia, unlike dogs and perhaps humans, show no augmentation of Hb concentration. Hypercapnia in rats also provokes much stronger Bohr effect than in dogs. Hypercapnia-induced Bohr effect in rats is accompanied with extreme desaturations of Hb-O2, and substantial reduction in the O2-carrying capacity. We speculate that the strong hypercapnia-induced Bohr effect in rats may prevent hypoxia at the tissue level. However, to maintain a stable oxygen-carrying capacity in rats used for pulmonary critical care studies with hypercapnia, we suggest to use hyperoxia, with or without a mild hypothermia.

Decreased Placental Transfusion may Lead to Persistent Pulmonary Hypertension of the Newborn (PPHN) 1156

Decreased Placental Transfusion may Lead to Persistent Pulmonary Hypertension of the Newborn (PPHN) 1156

378 Brain Differential Gene Expression in Neonatal Rats: Age- and Gender-Related Differences

BACKGROUND: Neonatal rats are used as animal models for neurological and developmental studies but possible age- or gender-related changes in their genomic profile are not known.OBJECTIVES: We tested the hypothesis that brain genomic profile could be different during the first days of life, depending on both gender and age.DESIGN/METHODS: Differential gene expression was tested in 3 groups of male and 3 groups of female pups (n=9 for each) randomly taken from 6 litters at birth and 3 and 10 days of age, respectively. At each age/gender category, pups were euthanized (pentobarbital) and whole brain was rapidly removed for microarray processing, using a 10K oligonucleotides rat array. Measurements from 9 samples in each group were taken at all 6 design points, leading to total of 27 slides. The slides were configured with extensive dye swaps to estimate dye bias and allow for precise (direct) estimation of simple period effects for gender and age. After slide-based normalization, gene-by-gene linear mixed models with random slide effects were fit using SAS Microarray solutions software package (Cary, USA). Bonferroni correction was used to control type-I error at an alpha level of 0.05.RESULTS: Statistically no significant differential gene expression occurred within the first 3 days after birth. At ten days of age, 45 genes were significantly up-regulated relative to birth and 21 genes were up-regulated relative to 3 days of age. No genes exhibited significant differential expression across genders up to 10 days.CONCLUSIONS: Whole brain genomic profile in neonatal rats is significantly modified at 10 days of age, whereas it may not be affected by gender at this early developmental period. The possibility that the genomic expression in specific neuroanatomical structures, as compared with whole brain, could be either age- or gender-related at an earlier developmental period, cannot be yet excluded.

Nitric oxide and Nitrogen dioxide Concentrations During In Vitro High Frequency Oscillatory Ventilation † 1970

Nitric oxide and Nitrogen dioxide Concentrations During In Vitro High Frequency Oscillatory Ventilation † 1970

Open-bridge Extracorporeal Membrane Oxygenation: a New Method of Weaning from ECMO 235

Introduction: The standard ECMO circuit has a bridge between the venous drainage and infusion tubing. This allows temporary dissociation of the patient from the ECLS circuit. Traditionally, while weaning from ECMO, pump and patient flows are not reduced below 100 ml/min for newborn and kept much higher in older children to prevent clotting in the circuit and the membrane oxygenator. These low flows during weaning may represent more than a third of the patients cardiac output. Trialing off of the patients from ECMO at these flows may fail. We have used an open-bridge technique to maintain high pump flows through the circuit and were able to reduce the patient flows to much lower rates and achieved a more stable and successful rate of decannulation. We are reporting the successful clinical application of partially opened bridge ECMO for weaning.

In Vitro Evaluation of Variability in Systemic Arterial Pressure Changes During Closed vs Open-bridge Extracorporeal Life Support 234

Introduction: Extracorporeal life support (ECLS) is used for the support of cardiorespiratory failure. The standard ECLS circuit has a bridge between venous drainage and infusion tubing. This allows temporary dissociation of the patient from the ECLS circuit. The bridge is opened intermittently to prevent clotting (called flashing). Changes in systemic arterial pressure (SAP) due to changes in systemic vascular resistance (SVR) have been reported during flashing of the bridge which can be avoided if the bridge is kept partially open. An in vitro method is developed to study variations in SAP during closed and open-bridge ECLS.