Amrinone versus dopamine and nitroglycerin in neonates after arterial switch operation for transposition of the great arteries

OBJECTIVE: To compare the efficacy and safety of amrinone and a combination of dopamine and nitroglycerin in neonates after reconstructive surgery for transposition of the great arteries. DESIGN: A prospective, randomized, double-blind study. SETTING: Pediatric intensive care unit in a university hospital. PARTICIPANTS: Thirty-five neonates with transposition of the great arteries. INTERVENTIONS: A loading dose of amrinone, 2 mg/kg, followed by a maintenance infusion of 7.5 microg/kg/min, were administered to 16 neonates before separation from cardiopulmonary bypass. The remaining 19 patients were administered a combination of dopamine, 5 microg/kg/min, and nitroglycerin, 1 microg/kg/min. An open-label epinephrine infusion was administered in both groups as required. MEASUREMENTS AND MAIN RESULTS: The circulatory state of the patients was evaluated from 4 to 18 hours after cardiopulmonary bypass. The systemic blood flow index, calculated using the Fick principle, was higher in the amrinone group (1.7+/-0.5 L/min/m2 [mean +/- SD]) compared with the dopamine-nitroglycerin group (1.4+/-0.4 L/min/m2; p < 0.04). The systemic vascular resistance in the amrinone group was lower (26+/-8 Wood units x m2) than in the dopamine-nitroglycerin group (35+/-12 Wood units x m2; p < 0.02). The oxygen extraction ratio was higher in the dopamine-nitroglycerin group (0.34+/-0.08) compared with the amrinone group (0.28+/-0.06; p < 0.02). Lower platelet counts were observed in the amrinone group, but no difference in hemorrhagic complications was seen between the groups. CONCLUSION: With the dosage regimen used, supplemented with epinephrine, amrinone provides a higher cardiac output and more favorable oxygen dynamics than a combination of dopamine and nitroglycerin.     

The efficacy of preemptive Milrinone or Amrinone therapy in patients undergoing coronary artery bypass grafting.

Acute deterioration in ventricular function and oxygen transport is common after cardiac surgery. We hypothesized that milrinone or amrinone may reduce their occurrence and catecholamine requirements and increase cellular enzyme levels in patients undergoing coronary artery bypass. In 45 patients, we randomly administered milrinone 50 microg/kg plus 0.5 microg x kg(-1) x min(-1) infusion for 10 h, amrinone 1.5 mg/kg plus 10 microg x kg(-1) x min(-1) infusion for 10 h, or placebo at release of aortic cross-clamp. Hemodynamic variables, dopamine requirement, and laboratory values were recorded. At the postoperative nadir, stroke volume index was higher in the Milrinone and Amrinone groups (mean +/- SD, 27.8 +/- 4.0 and 26.1 +/- 3.2 vs. 20.4 +/- 5.1 mL x min (-1) x m(-2) per beat, P < 0.0001), and oxygen transport index was higher (354.7 +/- 57.8 and 353.7 +/- 91.2 vs 283.0 +/- 83.9 mL. min(-1) x m(-2), P = 0.009). The postoperative dopamine requirement was less (6.6 +/- 2.7 and 6.8 +/- 2.6 vs 10.4 +/- 2.0 mg/kg, P < 0.008), and postoperative serum lactate, alanine and aspartate aminotransferase, lactate dehydrogenase, creatinine kinase, C-reactive protein, and glucose levels were less (P < 0.01). The mean postoperative heart rate was faster in the Milrinone group than in the Amrinone and Placebo groups (96.8 +/- 10.3 vs. 86.9 +/- 9.5 and 87.8 +/- 10.8 bpm, P < 0.01). Milrinone and amrinone administered preemptively reduce postoperative deterioration in cardiac function and oxygen transport, dopamine requirement, and increases in serum lactate, glucose, and enzyme levels, although milrinone may increase heart rate. IMPLICATIONS: Preemptive milrinone or amrinone administration before separation from cardiopulmonary bypass in cardiac surgical patients not only ameliorates postoperative deterioration in cardiac function and oxygen transport, but also reduces dopamine requirement and increases serum lactate, glucose, and cellular enzyme levels, although milrinone may increase heart rate.     

Efficacy of intravenous administration of atrial natriuretic peptide after cardiac surgery in neonates and infants]

Intravenous infusion of alpha-human atrial natriuretic polypeptide (hANP) and furosemide was performed in 12 patients (4: TGA, 3: univentricular heart, 3: HLHS, 2: VSD) after cardiopulmonary bypass. Their mean age at the operation was 68 days (6 patients in neonate), the mean body weight was 3.3 kg. All patients were treated with nitroglycerin in dose of 2 micrograms/kg/min and chlorpromazine in dose of 2.8 micrograms/kg/min and catecholamine in mean dose of 6.5 micrograms/kg/min. The criteria of indication for hANP was poor effect of furosemide alone. The hANP was given for 6-144 hours in dose of 0.1-0.2 microgram/kg/min. With the hANP and furosemide infusion, urine volume increased from 85.0 +/- 14.2 ml/kg/day to 107.9 +/- 25.3 ml/kg/day (p < 0.05), whereas the systemic arterial pressure, the central venous pressure and the renal function were unchanged. We conclude that the combination of the hANP and the furosemide is very effective in neonates and infants.     

Effect of amrinone on mucosal permeability in experimental intestinal ischaemia/reperfusion injury

BACKGROUND: The preventive effect of amrinone on ischaemia/reperfusion (I/R) injury has been shown in the medical literature. The purpose of the present study was to investigate the preventive effect of amrinone on I/R injury of the small bowel of the rat. METHODS: Thirty-two Wistar albino rats (140-180 g) were divided into four groups (n = 8). In all groups except the sham group the superior mesenteric artery was clamped for 30 min. At the beginning of reperfusion, 1 mL of 2405 Bq/mL 51Cr-ethylenediamine tetra-acetic acid (EDTA) was administered into the prepared ileal segment. Following 30 min of reperfusion, 1 mL of blood was obtained from the portal vein. After the rats were killed, the small intestine was removed for histopathological studies. A total of 5 mg/kg amrinone was administered to the rats in group 1 before ischaemia and in group 2 before reperfusion, whereas only saline was administered to the rats in the control group. Statistical analysis was carried out with Kruskal-Wallis and chi2 test, P < 0.01 was considered significant. RESULTS: Both the blood 51Cr-EDTA measurements (mean +/- SD) and mucosal injury grades (MIG) were highest in the control group (3.95 +/- 0.71 c.p.m.; MIG, 3-5) followed by group 2 (0.50 +/- 0.35 c.p.m.; MIG, 1-3), group 1 (0.47 +/- 0.34 c.p.m. MIG, 0-3), and sham group (0.12 +/- 0.05 c.p.m.; MIG, 0). The difference between groups 1 and 2 and the control group were statistically significant (P < 0.01 for each comparison). The results of group 1 and 2 were similar statistically (P > 0.05). CONCLUSIONS: Amrinone was found to be effective in preventing intestinal I/R injury.     

The effect of dopamine on glomerular filtration rate in normotensive,oliguric premature neonates

We examined the effect of dopamine on glomerular filtration rate (GFR) at infusion rates of 0.5, 2.5, and 7.5 micro g/kg per min in 15 premature neonates. Study infants (mean gestational age 34+/-2 weeks, mean birth weight 2.43+/-0.6 kg) had respiratory distress, were normotensive, and had a low urine output (0.9+/-0.1 ml/kg per hour). GFR was determined by the plasma clearance of inulin after a single bolus injection (200 mg/kg). Four hours after inulin administration, dopamine infusion was begun and continued over 6 h. GFR was estimated before and after beginning the dopamine infusions from the slope of the log of plasma inulin concentration versus time. Gestational age, weight, and baseline GFR were similar in all three groups. With a dopamine infusion rate of 0.5 micro g/kg per min there were no changes in GFR, urine output, heart rate, or blood pressure. At an infusion rate of 7.5 micro g/kg per min there was no change in GFR, although urine output, heart rate, and blood pressure all increased. At 2.5 micro g/kg per min there were significant increases in GFR and urine output, with no changes in blood pressure or heart rate. In oliguric, non-hypotensive neonates, GFR increased significantly at 2.5 micro g/kg per min of dopamine. This probably reflects the effects of afferent vasodilatation and may be important clinically when enhancement of GFR is the major treatment objective.     

Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures.

Remifentanil hydrochloride is an ultra-short-acting opioid that undergoes rapid metabolism by tissue and plasma esterases. We aimed to characterize the pharmacokinetics and determine the hemodynamic profile of remifentanil after a single-bolus dose in children aged 0 to 18 yr. Forty-two children undergoing elective surgical procedures received remifentanil 5 microg/kg infused over 1 min. Patients were divided into age groups as follows: young infants (< or =2 mo), older infants (> 2 mo to < 2 yr), young children (2 to < 7 yr), older children (7 to < 13 yr), adolescents (13 to < 16 yr), and young adults (16 to < 18 yr). Arterial blood samples were collected and analyzed by mass spectroscopy to determine remifentanil pharmacokinetic profiles. Hemodynamic measurements for remifentanil's effect were made after the infusion. Methods of statistical analysis included analysis of variance and linear regression, with significance at P < or = 0.05. Complete remifentanil pharmacokinetic data were obtained from 34 patients. The volume of distribution was largest in the infants < 2 mo (mean, 452 mL/kg) and decreased to means of 223 to 308 mL/kg in the older patients. There was a more rapid clearance in the infants < 2 mo of age (90 mL. kg(-1). min(-1)) and infants 2 mo to 2 yr (92 mL. kg(-1). min(-1)) than in the other groups (means, 46 to 76 mL. kg(-1). min(-1)). The half-life was similar in all age groups, with means of 3.4 to 5.7 min. Seven subjects (17%) developed hypotension related to the remifentanil bolus. Remifentanil showed an extremely rapid elimination similar to that in adults. The fast clearance rates observed in neonates and infants, as well as the lack of age-related changes in half-life, are in sharp contrast to the pharmacokinetic profile of other opioids. Remifentanil in a bolus dose of 5 microg/kg may cause hypotension in anesthetized children. IMPLICATIONS: The pharmacokinetics of remifentanil were studied in children from birth to 18 yr. Remifentanil was found to have age-related changes in clearance and volume of distribution, but not half-life. The increased clearance observed in young infants is in contrast to other opioids.     

High-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures

BACKGROUND: Since the time available to provide the cooling and rewarming is limited during deliberate mild hypothermia, the technique to accelerate the cooling and rewarming rate of core temperature has been studied. Amrinone has been reported to accelerate the cooling rate but not the rewarming rate of core temperature during deliberate mild hypothermia. The failure of amrinone effect on the rewarming rate might be due to an insufficient dose of amrinone during hypothermic conditions. The authors therefore tested whether higher doses of amrinone can accelerate the rewarming rate of core temperature during deliberate mild hypothermia for neurosurgery. METHODS: After institutional approval and informed consent, 30 patients were randomly assigned to one of three groups. Patients in the control group (n = 10) did not receive amrinone; patients in the AMR 15 group (n = 10) received 15 microg x kg(-1) x min(-1) amrinone with a 1.0-mg/kg loading dose of amrinone at the beginning of cooling; and patients in the ReAMR group (n = 10) received 5 microg x kg(-1) x min(-1) amrinone with 1.0-mg/kg loading and reloading doses of amrinone at the beginning of cooling and rewarming, respectively. Administration of amrinone was started just after the induction of cooling and continued until the end of anesthesia. Anesthesia was maintained with nitrous oxide in oxygen, propofol, and fentanyl. After induction of anesthesia, patients were cooled, and tympanic membrane temperature was maintained at 34.5 degrees C. After completion of the main surgical procedures, patients were actively rewarmed and extubated in the operating room. RESULTS: The cooling and rewarming rates of core temperature were both significantly faster in both amrinone groups than in the control group. During the cooling and rewarming periods, forearm minus fingertip temperature gradient was significantly smaller in both amrinone groups than in the control group. During the rewarming period, heart rate and mean arterial pressure in the AMR 15 group were significantly faster and lower, respectively, than in the control group. Systemic vascular resistance in the AMR 15 group was smaller than in the control group throughout the study; on the other hand, only the value after the start of rewarming in the ReAMR group was smaller than in the control group. CONCLUSIONS: Amrinone at an infusion rate of 15 or 5 microg x kg(-1) x min(-1) with a reloading at the beginning of rewarming accelerated the rewarming rate of core temperature during deliberate mild hypothermia. This suggests that high-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures.     

Effect of continuous infusion of prostaglandin E1 on hepatic blood flow.

STUDY OBJECTIVE: To evaluate the effects of an intravenous infusion of prostaglandin E1 (PGE1) on hepatic blood flow. DESIGN: Prospective clinical study. SETTING: University-affiliated hospital. PATIENTS: 16 ASA physical status I and II surgical patients who were scheduled for abdominal surgery. INTERVENTIONS: Patients were anesthetized with 1% sevoflurane and 66% nitrous oxide. PGE1 0.05 mg/kg/min or PGE1 0.10 mg/kg/min was continuously infused, followed by an infusion of 1000 mL Ringer's acetate solution. MEASUREMENTS: The hemodynamic effect of PGE1 was examined using pulse dye densitometry (PDD). A nose probe for PDD was used, and 10 mg indocyanine green (ICG) in 2 mL distilled water was bolus-infused into a central venous catheter for each measurement. Cardiac output (CO), circulating blood volume (CBV), and plasma dye clearance rate (K) were monitored from the dye-densitogram. Hepatic blood flow was estimated using the K and CBV values. MAIN RESULTS: PGE1 did not increase CBV or CO. Even adding a 1000 mL crystalloid infusion did not expand CBV, whereas mean arterial pressure (MAP) significantly decreased from 91.1 +/- 16.5 mmHg to 84.8 +/- 13.5 mmHg (PGE1 0.05 microg/kg/min) and 80.6 +/- 14.4 mmHg (PGE1 0.10 microg/kg/min ) (p < 0.01 compared with control value), then to 72.0 +/- 6.5 mmHg (PGE1 0.10 microg/kg/min + 1000 mL Ringer's acetate) (p < 0.01 compared with control value). Hepatic blood flow changes were 1.46 +/- 0.60 L/min (control), 1.48 +/- 0.45 L/min (PGE1 0.05 microg/kg/min), 1.14 +/- 0.35 L/min (PGE1 0.10 microg/kg/min), and 1.15 +/- 0.19 L/min (PGE1 0.10 microg/kg/min + 1000 mL Ringer's acetate) (no significant difference, p < 0.05). Hepatic blood flow and K values did not statistically significantly differ at each condition. CONCLUSIONS: PGE1 does not affect blood volume shift, CO, or hepatic blood flow.     

Pharmacodynamics and pharmacokinetics of high-dose sufentanil in infants and children undergoing cardiac surgery

The pharmacodynamic and pharmacokinetic profiles of high-dose sufentanil (15 micrograms/kg) and oxygen were determined in 20 infants and children undergoing repair of congenital heart defects. Sufentanil provided marked hemodynamic stability after an infusion and during the stress periods of incision and sternotomy. Two patients required supplemental nitrous oxide because of an increase in blood pressure greater than 20% of baseline. Mean plasma catecholamine concentrations varied widely among patients and increased, although not significantly, during intraoperative stress. Pharmacokinetic data best fit a two-compartment model. In infants younger than 10 months (group 1) and children older than 10 months (group 2) who were not surface-cooled, elimination half-lives were similar (mean +/- SD, 53 +/- 15 min vs 55 +/- 10 min) as were clearance values (27.5 +/- 9.3 vs 18.1 +/- 10.7 ml X kg-1 X min-1). However, the volumes of distribution were significantly smaller in group 1 compared with group 2 (1.6 +/- 0.46 vs 3.0 +/- 1.3 L/kg). In infants younger than 10 months who were surface-cooled (group 3) elimination half-life was longer (120 +/- 36 min) and volume of distribution larger (3.7 +/- 1.1 L/kg), but clearance rate was similar (21.5 +/- 5.0 ml X kg-1 X min-1) compared with age- and weight-matched infants (group 1).     

Intravenous flecainide for the treatment of junctional ectopic tachycardia after surgery for congenital heart disease

BACKGROUND: Junctional ectopic tachycardia (JET) is a life-threatening arrhythmia producing severe hemodynamic dysfunction, which may complicate the postoperative course of surgery for congenital heart disease. Strict care and a fast and effective antiarrhythmic strategy are essential, because mortality largely depends on the duration of the arrhythmia. METHODS: Seven consecutive neonates with postoperative JET without any evidence of myocardial ischemia received intravenous flecainide after conventional therapies proved ineffective. Atrial pacing at the minimal rate for atrioventricular synchrony was followed by a 10-min intravenous infusion of 1.6 mg/kg flecainide, then continuous infusion of 0.4 mg/kg flecainide per hour. Treatment was considered effective based on restoration of sinus rhythm or a JET rate no higher than 170 bpm within 4 hours of flecainide loading. Overall mean flecainide infusion lasted 31.2 hours (range 25 to 53 hours). Side effects were assessed by monitoring plasma flecainide levels, electrocardiogram, arterial pressure, and central venous pressure. RESULTS: Flecainide was effective in all 7 patients after an infusion duration of 3.6 +/- 1.5 hours. Sinus rhythm was restored after 7.2 +/- 9.7 hours. After 4 hours of loading, heart rate fell from 219 +/- 14 to 136 +/- 7 bpm (p < 0.0001), arterial pressure increased from 69 +/- 8 to 93 +/- 10 mm Hg (p < 0.0001), while central venous pressure decreased from 8.0 +/- 1.6 to 5.2 +/- 1.9 mm Hg (p = 0.0007). No side effect or recurrence was noted. CONCLUSIONS: Flecainide can exert a fast antiarrhythmic effect on postoperative JET, and its infusion can be modulated to maintain the concentration within the therapeutic range, thus avoiding toxicity. We propose further consideration of flecainide for treatment of JET in neonates without myocardial ischemia.     

Amrinone reverses cardiac depression and augments coronary vasodilation with isoflurane in the isolated heart

Amrinone is a positive inotropic and vasodilatory agent and may be administered during anesthesia with isoflurane. The authors' aims were 1) to examine if amrinone produces coronary artery vasodilation through an increase in metabolic demand or through a direct vasodilatory effect or through both and 2) to test if amrinone attenuates cardiac depression and enhances coronary artery vasodilation produced with exposure to isoflurane. The effects of these drugs were examined in 11 isolated perfused guinea pig hearts. Variables measured were: heart rate (HR), atrioventricular conduction time (AVCT), isovolumetric peak left ventricular pressure (LVP), coronary flow, percent O2 extraction, myocardial O2 consumption (MVO2), and the ratio of O2 delivery (DO2) to MVO2. Each heart was exposed for 10-min periods to 10, 50, 100, and 500 microM amrinone alone, and to 0.5 or 1% isoflurane before, during, and after amrinone. Initial control values were: heart rate 216 +/- 5 beats per min; AVCT 56 +/- 1 ms; peak LVP 86 +/- 3 mmHg; coronary flow 6.3 +/- 0.3 ml.min-1.g-1 (11.4 +/- 0.7 ml.min-1.g-1 with adenosine bolus), percent O2 extraction 52 +/- 3%; DO2 107 +/- 3 microliters.min-1.g-1; MVO2 56 +/- 4 microliters.min-1.g-1; and DO2/MVO2 1.75 +/- 0.08. Amrinone 500 microM alone increased (P less than 0.05) heart rate by 9%, LVP by 13%, coronary flow by 18%, and MVO2 by 23%; AVCT decreased by 3%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prophylactic amrinone for weaning from cardiopulmonary bypass

This prospective, randomised, double-blind, controlled clinical study was performed at a single tertiary referral centre to test the hypothesis that the prophylactic administration of amrinone before separation of a patient from cardiopulmonary bypass decreases the incidence of failure to wean, and to identify those patients who could be predicted to benefit from such pre-emptive management. Two hundred and thirty-four patients, scheduled to undergo elective cardiac surgery, were randomly allocated to receive either a bolus dose of 1.5 mg x kg(-1) amrinone over 15 min, followed by an infusion of 10 microg x kg(-1) x min(-1), or a bolus of placebo of equal volume followed by an infusion of placebo. Treatment with amrinone or placebo was initiated upon release of the aortic cross-clamp, before weaning from cardiopulmonary bypass. Anaesthetic technique, monitoring and myocardial preservation methods were standardised for both groups. Significantly fewer patients failed to wean in the group that received prophylactic amrinone than in the control group (7 vs. 21%, p = 0.002). Amrinone improved weaning success regardless of left ventricular ejection fraction, although this benefit was statistically significant only in the group with left ventricular ejection fractions > 55%. Of the 32 patients who failed to wean from cardiopulmonary bypass, 14 had normal pre-operative left ventricular ejection fractions.     

Elimination Rate Constant Describing Clearance of Infused Fluid from Plasma Is Independent of Large Infusion Volumes of 0.9% Saline in Sheep

Background: The purpose of this study was to determine the influence of varying large crystalloid infusion volumes, ranging from a volume that has been safely administered to volunteers to a volume that greatly exceeds a practical volume for studies in normovolemic humans, of rapidly infused 0.9% saline on the elimination rate constant in sheep.

Methods: Six sheep underwent three randomly ordered, 20 min, intravenous infusions of 0.9% saline in volumes of 25 ml/kg, 50 ml/kg and 100 ml/kg. Repeated measurements of arterial plasma dilution were analyzed using the volume kinetic approach to determine the apparent volumes of the central (V1) and peripheral (V2) body fluid spaces, the elimination rate constant (kr) describing clearance from the central fluid space and the rate constant (kt) for the diffusion of fluid between the central and the peripheral fluid spaces. The latter constant was split in to two constants, one describing flow out from the central fluid space and one describing flow into the central fluid space. Urinary output was measured in all sheep.

Results: kr was comparable at each infused volume (38.3 +/- 4.5, 32.2 +/- 4.2, and 36.7 +/- 7.0 ml/min, respectively, in the 25 ml/kg, 50 ml/kg, and 100 ml/kg protocols). However, for the largest infusion, other kinetic parameters were influenced by the magnitude of the infusion. V2 was significantly increased (P < 0.05) and the area under the dilution-time curve divided by the infused volume was 20% lower for the largest infusion (P < 0.03). Although urinary output increased as the infusion volume increased, only 59% of the administered volume had been excreted at 180 min after the 100 ml/kg infusion as compared with approximately 90% after the other two infusions (P < 0.01).     

Combined prostaglandin therapy and ductal formalin infiltration in neonatal pulmonary oligemia

Prostaglandins and ductal formalin infiltration, singly and together, have been used in efforts to improve pulmonary flow in very ill newborn infants with right ventricular outflow tract obstruction. To evaluate the efficacy of concurrent use of prostaglandins and ductal formalin infiltration, we have reviewed our experience with 25 infants with right ventricular outflow tract obstruction and prostaglandin-ductal formalin infiltration therapy. Prostaglandin therapy was begun 22 +/- 21 hours (range 20 to 93 hours) before and was continued 20 +/- 18 hours (range 0 to 62 hours) following ductal formalin infiltration; prostaglandin administration was initiated at a dose of 0.05 to 0.1 microgram/kg/min and tapered postoperatively. Clinical cyanosis was diminished in 20 of 25 infants (80%) postoperatively. Systemic arterial pH and oxygen saturation both improved following prostaglandin-ductal formalin infiltration therapy from 7.35 to 7.41 (p less than 0.001) and from 35.7 to 50.3 (p less than 0.001), respectively. Persistent ductal patency (mean 219 +/- 191 days) was observed in 17 survivors of the early postoperative period (more than 14 days). Two of five infants who died within 14 days of operation had a widely patent ductus with resultant progressive congestive heart failure. The other three infants died as a result of operative technical problems, dysrhythmias, and thrombotic ductal closure, respectively. No correlation was observed between duration of ductus patency and operatively determined size of ductus, total prostaglandin dose, or duration of prostaglandin infusion. Secondary operative intervention was delayed by 92 +/- 74 days with prostaglandin-ductal formalin infiltration therapy; thus prostaglandin-ductal formalin infiltration therapy may have a role in selected neonates with right ventricular outflow tract obstruction.     

Amrinone versus dopamine-nitroglycerin after reconstructive surgery for complete atrioventricular septal defect

To compare the effectiveness and safety of amrinone and a combination of dopamine and nitroglycerin in infants after reconstructive surgery for congenital heart disease. A prospective, randomized, double-blind study. Pediatric intensive care unit in a university hospital. Thirty-two infants with complete atrioventricular septal defect. Amrinone loading dose, 2 mg/kg, followed by a maintenance infusion, 7.5 μg/kg/min, was given to 17 infants before separation from cardiopulmonary bypass. The remaining 15 patients received a combination of dopamine, 5 μg/kg/min, and nitroglycerin, 1 μg/kg/min. The circulatory state of the patients was evaluated from 4 to 18 hours after cardiopulmonary bypass. The systemic blood flow index, calculated using the Fick principle, was higher in the amrinone group (2.5 ± 0.7 L/min/m²) compared with the dopamine-nitroglycerin group (2.0 ± 0.6 L/min/m², mean ± SD). The pulmonary blood flow index in the amrinone group was higher (2.9 ± 0.6 L/min/m²) than in the dopaminenitroglycerin group (2.2 ± 0.6 L/min/m²); no significant difference was noted in the mean pulmonary artery pressure. The oxygen extraction ratio was higher in the dopamine-nitroglycerin group (0.41 ± 0.07) compared with the amrinone group (0.34 ± 0.08). Despite lower platelet counts in the amrinone group, no hemorrhagic complications were seen in any patient. With this dosage regimen, amrinone provides a higher cardiac output, more favorable oxygen dynamics, and lower pulmonary vascular resistance than dopamine and nitroglycerin.     

The effect of insulin infusion upon protein metabolism in neonates on extracorporeal life support

OBJECTIVE: Critically ill neonates on extracorporeal life support (ECLS) demonstrate elevated rates of protein breakdown that, in turn, are associated with increased morbidity and mortality. This study sought to determine if the administration of the anabolic hormone insulin improved net protein balance in neonates on ECLS. METHODS: Twelve parenterally fed neonates, on ECLS, were enrolled in a randomized, prospective, crossover trial. Subjects were administered a hyperinsulinemic euglycemic clamp and a control saline infusion. Protein metabolism was quantified using ring-D5-phenylyalanine and ring-D2-tyrosine stable isotopic infusions. Statistical comparisons were made by paired sample t tests (significance at P < 0.05). RESULTS: Serum insulin concentration increased 20-fold during insulin infusion compared with saline infusion control (P < 0.0001). Protein breakdown was significantly decreased during insulin infusion compared with controls (7.98 +/- 1.82 vs. 6.89 +/- 1.03 g/kg per day; P < 0.05). Serum amino acid concentrations were significantly decreased by insulin infusion (28,450 +/- 9270 vs. 20,830 +/- 8110 micromol/L; P < 0.02). Insulin administration tended to decrease protein synthesis (9.58 +/- 2.10 g/kg per day vs. 8.60 +/- 1.20; P = 0.05). For the whole cohort, insulin only slightly improved net protein balance (protein synthesis minus protein breakdown) (1.60 +/- 0.80 vs. 1.71 +/- 0.89 g/kg per day; P = 0.08). In neonates receiving > or =2 g/kg per day of dietary amino acids insulin significantly improved net protein balance (2.17 +/- 0.34 vs. 2.40 +/- 0.26 g/kg per day; P < 0.01). CONCLUSIONS: Insulin effectively decreases protein breakdown in critically ill neonates on ECLS. However, this is associated with a significant reduction in plasma amino acids and a trend toward decreased protein synthesis. Insulin administration significantly improves net protein balance only in those ECLS neonates in whom adequate dietary protein is provided.     

Pharmacokinetics of amrinone during cardiac surgery.

Amrinone is a nonglycosidic noncatecholamine with both vasodilator and positive inotropic effects that may be administered to patients undergoing cardiac surgery. As an initial step toward elucidating the optimal dosage of amrinone for cardiac surgical patients we studied the pharmacokinetics of amrinone during and after cardiac surgery requiring cardiopulmonary bypass. The study population comprised 35 adult patients, each receiving a single dose of amrinone (0.75, 1.5, 2.0, or 2.5 mg/kg) administered into the venous reservoir near the end of cardiopulmonary bypass. Additionally, 15 of the 35 patients also received intravenous infusions of either 5 or 10 micrograms.kg-1.min-1. Arterial blood was sampled over the next 22 h, and plasma concentrations of amrinone were determined by high-performance liquid chromatography. Protein binding of amrinone, assayed by equilibrium dialysis, was 21.6 +/- 2.5%. The decay of amrinone concentrations in plasma over time was fit to a biexponential equation by nonlinear least-squares regression. The manufacturer's recommended dose of 0.75 mg/kg followed by an infusion of 10 micrograms.kg-1.min-1 was inadequate to maintain the plasma concentration within the therapeutic range based on the pharmacodynamics of amrinone in patients with chronic congestive heart failure. This was due to significant redistribution of amrinone in the body after the loading dose. To maintain a therapeutic plasma concentration of 1.5-2.0 micrograms/ml, a larger loading dose or a supplemental loading dose as well as a continuous infusion is required.     

Cerebral ischemia caused by obstructed superior vena cava cannula is detected by near-infrared spectroscopy

OBJECTIVE: Bicaval venous cannulation is being used with increasing frequency in neonates and infants to avoid circulatory arrest. However, superior vena cava (SVC) cannula obstruction may result in cerebral ischemia with no change in blood pressure or mixed venous O2 saturation. The authors hypothesized that near-infrared spectroscopy (NIRS) would allow noninvasive detection of SVC cannula obstruction. METHODS: Fifteen Yorkshire piglets (9.07 +/- 0.20 kg) underwent total cardiopulmonary bypass (CPB) (100 mL/kg/min, pH-stat strategy, hematocrit of 20%) with ascending aortic and bicaval cannulations. Femoral arterial and SVC pressure were monitored as well as mixed venous O2 saturation. NIRS monitoring of tissue oxygenation index (TOI) as well as oxyhemoglobin and deoxyhemoglobin (HHb) was undertaken. Animals were cooled to an esophageal temperature of 25 degrees C over 20 minutes. CPB flow was reduced to 50 mL/kg/min for 20 minutes. Animals then underwent a 60-minute study period of continuous CPB at 50 mL/kg/min with manipulation of the SVC cannula: group 1, open; group 2, partial occlusion; and group 3, complete occlusion. Animals were rewarmed to 37 degrees C at full flow with the SVC cannula open. Cerebral blood flow was assessed at onset of CPB, at end of cooling, at end of low flow, at end of SVC manipulation period, and at end of rewarming using radioactive microspheres. RESULTS: CBF decreased to 27.9 +/- 1.5 mL/min/100 g with complete occlusion (p < 0.01 v group 1: 39.7 +/- 1.9, group 2, 38.3 +/- 2.0 mL/min/100 g) with no change in arterial pressure or mixed venous saturation. There were also significant differences in cerebral oxygen delivery between group 3 and other groups (p < 0.01). SVC pressure increased to 19.5 +/- 4.5 and 32.5 +/- 3.1mmHg with partial and complete occlusion. NIRS indicated significant cerebral ischemia with a decrease in TOI (p < 0.05; group 3 v group 1 and 2) and an increase in HHb (p < 0.05; group 3 v group 1). At the end of the study, significant acidosis was found in group 3 compared with group 1 (p < 0.05). CONCLUSION: SVC cannula obstruction causes cerebral ischemia with no change in blood pressure or venous oxygen saturation. In view of the difficulties and risks of CVP monitoring in babies, it is recommended to use other monitoring modalities such as NIRS to assess adequacy of cerebral perfusion if bicaval cannulation is used in neonates and infants.     

Pharmacokinetics of bupivacaine following intraoperative intercostal nerve block in neonates and in infants aged less than 6 months

Pharmacokinetics and blood concentrations of bupivacaine were studied after intercostal nerve blocks were performed intraoperatively using 1.5 mg.kg-1 in 11 neonates (age 0-28 days) and 11 infants between age 1 and 6 months. The study aimed to provide pharmacokinetic data that are limited in these age groups, and to identify any adverse effects of intercostal nerve block in infancy. Arterial blood samples were taken at 0, 5, 10, 15, 20, 30, 60, 120, 240, and 360 min. Whole blood bupivacaine was assayed by high-performance liquid chromatography. Peak blood concentrations were attained within 10 min in 18 of 22 subjects, and were 087 micrograms.ml-1 [corrected] +/- 0.56 micrograms.ml-1 (mean and SD) and 0.91 +/- 0.27 micrograms.ml-1 in neonates and infants, respectively. Pharmacokinetic variables in the two groups included elimination half-life (t1/2 beta): 132 +/- 59 min and 102 +/- 39 min; steady-state volume of distribution (Vdss): 2.56 +/- 0.76 l.kg-1 and 2.17 +/- 0.17 l.kg-1; and total body clearance (Clt): 16.93 +/- 9.32 ml.min-1.kg-1 and 15.71 +/- 6.99 ml.min-1.kg-1. There was no statistically significant difference between neonates and infants with regard to any of these parameters. Patients were further divided into those with acyanotic and cyanotic disease. Cyanotic infants were significantly heavier than acyanotic infants (P less than 0.05), but no other differences were demonstrated. No adverse effects resulting from the technique were identified.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vecuronium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children

PURPOSE: To determine the effect of moderate and deep hypothermic cardiopulmonary bypass (CPB) on the pharmacokinetic and pharmacodynamic behaviour of vecuronium in infants and children. METHODS: We studied 12 patients undergoing surgery for congenital heart disease under narcotic-nitrous oxide anesthesia. Neuromuscular blockade was maintained constant (TI 4-10% by Datex electromyograph) by adjusting a vecuronium infusion. Plasma vecuronium concentrations (Cpss) were analysed by HPLC to describe a pseudosteady-state during each of the pre-CPB, CPB and post-CPB phases. Paired arterial blood samples were taken 20 min apart after at least 20 min of constant infusion. RESULTS: Nine cases were analysed, mean age 20 mo, mean weight 9 kg. Three patients had deep and six moderate hypothermia. In the pre-CPB phase Cpss fell into two groups (mean +/- SD: 330 +/- 42 ng x ml(-1); 127 +/- 27 ng x ml(-1); P < 0.001); similarly the clearances showed a bimodal distribution (mean +/- SD: 5.08 +/- 0.94; 11.51 +/- 0.2 ml x min(-1) x kg(-1) P < 0.001), although in different patients. During CPB this bimodal distribution disappeared. Vecuronium infusion rate (VIR) decreased by 84% and 92% from pre-CPB to CPB phase in deep and moderate hypothermia groups respectively (P < 0.05), paralleled by decreases in Cpss of 36% (P > 0.05) and 52% (P < 0.05). CONCLUSION: Changes in vecuronium requirements and plasma concentrations during CPB demonstrate that vecuronium pharmacokinetics and pharmacodynamics are both affected by hypothermic CPB in infants. The finding of bimodal distributions for plasma vecuronium and vecuronium clearance highlights the need for individual monitoring of neuromuscular blockade in this age group.