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Biomedical subjects

A M Lynn

Publications and source records attributed to A M Lynn.

At least 37 records · Page 2Linked to original sources

Hemodynamic effects of amrinone in children after Fontan surgery.

After Fontan repair in children, we performed a prospective, open-label study to evaluate the effect of amrinone on pulmonary vascular resistance (PVRI). Eight patients who underwent the Fontan repair had baseline arterial pressure, left atrial pressure, central venous pressure, and cardiac output measured postoperatively. Hemodynamic measurements were repeated after amrinone 4.5 mg/kg. The PVRI tended to decrease, but the change was not statistically significant. Although the systemic vascular resistance decreased to 802 +/- 222 from 941 +/- 191 dynes.s.cm-5.m-2 (P < 0.05), mean arterial blood pressure was unchanged. Cardiac index (3.8 +/- 1.2 to 4.7 +/- 1.6 L.min-1.m-2) and stroke volume index (23.6 +/- 6.7 to 30.5 +/- 8.1 mL.beat-1.m-2) increased, and heart rate decreased (160 +/- 21 to 151 +/- 24 bpm) (P < 0.05). Colloid transfusion during amrinone bolus administration was 13.9 mL/kg. The mean serum amrinone concentration was 4.2 micrograms/mL at the end of bolus and clearance was 2.24 mL.kg-1.min-1. Arrhythmias and thrombocytopenia were not noted. We conclude that amrinone administration is effective in increasing cardiac output in children who have undergone a Fontan repair.

Amrinone↗

Amrinone loading during cardiopulmonary bypass in neonates, infants, and children.

OBJECTIVES: To determine whether amrinone is bound to cardiopulmonary bypass circuits. When amrinone is administered to children during cardiopulmonary bypass, determine whether measured amrinone concentrations differ from those predicted based on a reported volume of distribution of 1.6 L/kg. DESIGN: In vitro study: Uptake of amrinone by cardiopulmonary bypass circuits was determined. Clinical study: Prospective, open label investigation. SETTING: University-affiliated tertiary children's hospital. PARTICIPANTS: Clinical study: 27 children participated, including 5 neonates and 9 infants. INTERVENTIONS: In vitro study: Waste blood was circulated within seven pediatric cardiopulmonary circuits. Amrinone was administered, and blood was serially assayed for amrinone levels. Clinical study: Amrinone (mean dose 4.9 mg/kg) was loaded during cardiopulmonary bypass and amrinone concentrations in pump blood were determined at termination of bypass. Amrinone measured by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary bypass circuit uptake reduced amrinone concentrations to 79% of predicted. After correcting for circuit uptake, serum amrinone levels in patients were significantly higher than predicted. The levels, expressed in the ratio of measured: predicted amrinone concentration, did not differ among neonates, infants, and children older than 1 year of age. CONCLUSIONS: When amrinone is administered to children during cardiopulmonary bypass, about 20% of the dose becomes bound to the circuit. Available drug is distributed within a smaller volume than predicted. This may be the consequence of the physiologic perturbations of hypothermic cardiopulmonary bypass.

Amrinone↗

Towards 2000.

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Dental Auxiliaries↗

Hemodynamic effects of amrinone and colloid administration in children following cardiac surgery.

Amrinone was used as the sole vasoactive medication in 9 of 14 children (aged 5 months to 8.25 years) given the drug following open repair of congenital cardiac lesions. Four children received a concomitant dopamine infusion and one infant had the infusion stopped after 5 hours for low mean arterial pressure (49 mmHg). In the 10 children receiving only amrinone, cardiac index increased 21% (range, 0 to 94%) after a total loading dose of 4.5 mg/kg given over 1 hour. Four of 14 patients (29%) required dopamine infusions to maintain mean arterial pressure over 55 mmHg and in these children cardiac index increased from baseline and was maintained during the amrinone infusion. Preload was held constant by administration of whole blood or plasmanate during amrinone loading; a decrease in systemic vascular resistance index was seen resulting in a stable arterial blood pressure. Minimal chronotropic effect was seen and no arrhythmias occurred. The sole child with postoperative pulmonary hypertension had a beneficial decrease in pulmonary artery pressure, increase in cardiac index, and stable systemic blood pressure during amrinone use. Cardiac index changes during amrinone loading in these children were variable and less clearly related to serum levels than reported in adults. Pharmacokinetic analysis in 12 children showed a clearance of 3.4 mL/min/kg, a volume of distribution of 1.65 L/kg, and an elimination half-life of 5.75 hours. Decreases in platelet counts were seen in 6 children and platelet transfusion was needed in 1; thus, serial platelet counts should be monitored.(ABSTRACT TRUNCATED AT 250 WORDS)

Amrinone↗

Respiratory effects of intravenous morphine infusions in neonates, infants, and children after cardiac surgery.

We evaluated the respiratory effects of intravenous morphine infusions in 30 patients (2 to 570 days old, mean 155 days) after cardiac surgery. PaCO2 during spontaneous breathing and CO2 response curves during rebreathing were obtained on morphine infusions at drug steady state and during drug washout. Steady state morphine serum levels > 20 ng/mL resulted in hypercarbia (PaCO2 > 55 mm Hg) and depressed CO2 response curve slopes (< 10 mL.min-1.mm Hg ETCO2(-1).kg-1) in 67% and 70% of patients, respectively (P < 0.05, compared to those with levels < 20 ng/mL). During washout, morphine levels more than 15 ng/mL resulted in hypercarbia in 46%, whereas levels less than 15 ng/mL were associated with hypercarbia in 13% (P = 0.025). No age-related differences in respiratory effect were seen in these studies at the same serum morphine level. Careful observation of any patient receiving morphine remains necessary, but neonates and young infants seem to have the same respiratory response to morphine infusions as older infants and children at the same blood level.

Cardiac Surgical Procedures↗

Disposition and respiratory effects of intrathecal morphine in children.

BACKGROUND: The extent and duration of respiratory depression after opioid administration are poorly defined in infants and children. METHODS: The disposition and respiratory effects of intrathecal morphine were studied in ten patients (ages 4 months-15 yr) after repair of craniofacial defects. Morphine, 0.02 mg/kg, was administered intrathecally before the end of surgery. Postoperatively, we determined the minute ventilation (VE) in response to increasing partial pressure of end-tidal carbon dioxide (PETCO2) during carbon dioxide rebreathing. The slope (VE/PETCO2) and intercept (VE at PETCO2 60 mmHg, VE 60) of the carbon dioxide response curve were calculated at 6, 12, and 18 h after morphine administration. Cerebrospinal fluid (CSF) and blood were analyzed for morphine concentration by radioimmunoassay. RESULTS: Mean VE/PETCO2 decreased from a preoperative value of 35.1 +/- 3.7 to 16.3 +/- 2.8 ml.kg-1 x min-1 x mmHg-1 at 6 h after morphine, and remained depressed to 23.4 +/- 2.9 and 23.5 +/- 3.3 ml.kg-1 x min-1 x mmHg-1 at 12 h and 18 h, respectively, compared to preoperatively). The infants' (n = 3) VE/PETCO2 at 6 h were 21, 4, and 27 ml.kg-1 x min-1 x mmHg-1. Mean VE 60 decreased from 874 +/- 125 to 276 +/- 32 ml x kg-1 x min-1 at 6 h, but then recovered at 12 and 18 h to 491 +/- 68 and 567 +/- 82 ml.kg-1 x min-1, respectively. The infants' VE 60 at 6 h were 350, 142, and 245 ml.kg-1 x min-1. Mean CSF morphine concentration was 2,860 +/- 540 ng/ml at 6 h, and decreased to 640 +/- 220 and 220 +/- 150 ng/ml at 12 and 18 h, respectively. CONCLUSIONS: Intrathecal morphine, 0.02 mg/kg, depressed the ventilatory response to carbon dioxide for up to 18 h concomitant with increased CSF morphine concentrations. Infants (4-12 months of age) did not exhibit greater ventilatory depression than did children (2-15 yr of age).

Administration, Inhalation↗

The maturation of morphine clearance and metabolism.

OBJECTIVE: To determine how early in childhood the clearance of morphine sulfate reaches that in adults. DESIGN: Patient series. SETTING: Children's Hospital and Medical Center, Seattle, Wash. PARTICIPANTS: Forty-nine children aged 1 day to 2.5 years with normal renal and hepatic function. All children were receiving a constant rate intravenous infusion of morphine for postoperative analgesia for greater than 24 hours. INTERVENTIONS: Blood and urine samples were collected during infusion and immediately after discontinuation of the morphine infusion. MEASUREMENTS: Morphine concentrations were determined and clearance was calculated using the infusion data. Half-life and volume of distribution were calculated using the postinfusion data. The formation of metabolites was evaluated using the urine data. Morphine clearance increased with age, median clearances ranging from 5 mL/kg per minute in neonates aged 1 to 7 days to 21 mL/kg per minute in infants aged 6 months and older. This change in clearance correlated with age. The formation clearance of morphine glucuronide was correlated with age, whereas the formation clearance of morphine sulfate and the renal clearance of morphine were independent of age. CONCLUSIONS: Morphine clearance reaches adult values by age 6 months to 2.5 years. In contrast to previous reports on the maturation of sulfate conjugation, it does not appear that morphine sulfate clearance is enhanced relative to glucuronidation in early infancy.

Analgesia↗

After the contract ... which way now?

There can be little doubt that the treadmill of NHS dentistry has done little to improve standards, and one can only applaud those who are so actively seeking to do so. But, perhaps sometimes we should examine our motives. Why do we want to improve? We cannot all hope to provide the very best for everyone. There simply are not the funds or the dentists. Is it so that we can obtain more money, or greater job satisfaction, or to give the patient a better deal?

Dental Auxiliaries↗

Age-dependent morphine partitioning between plasma and cerebrospinal fluid in monkeys.

Steady-state partitioning of morphine between blood and cerebrospinal fluid (CSF) was evaluated in pigtailed monkeys at three ages: 2-3 days, 1 month and 1 year. Protein binding of morphine to serum proteins was assessed by ultrafiltration. Newborns showed a higher CSF to plasma ratio than the 1-month- or 1-year-old monkeys (0.506 vs. 0.369 or 0.374, respectively). Protein binding of morphine was 11% in newborns, and 17% at 1 year of age, not explaining the increased morphine penetration into CSF in newborns. Increased CSF morphine is a transient finding in infant macaques, which appears to reach young adult values by 1 month of age.

Aging↗

Pharmacokinetics and pharmacodynamics of morphine in infant monkeys.

We report the pharmacokinetics of morphine administered as intravenous boluses in newborn (less than 7 days) and 3- to 4-month-old macaque monkeys. Morphine was administered in a series of bolus doses until PaCO2 was elevated greater than 50 mm Hg. In newborns less than 7 days of age, a mean dose of 1.4 mg/kg was required (range 0.75-2.8 mg/kg), and in the 3-month-olds, a mean dose of 1.88 mg/kg was required (range 1.5-2.5 mg/kg). The respiratory effects measured by PaCO2 and respiratory rate did not correlate with declining serum or cerebrospinal fluid morphine levels. Both newborn and 3- to 4-month-old macaque monkeys show only mild respiratory depression after intravenous morphine, at serum concentrations as high as 300-400 ng/ml. Infant and young macaque monkeys appear to be less sensitive to the respiratory depressant effect of morphine than humans.

Aging↗

From Black to White.

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Dental Restoration, Permanent↗

Short-acting barbiturate sedation: effect on arterial pH and PaCO2 in children.

One hundred and fifteen unpremedicated children, induced with thiamylal, a short-acting thiobarbiturate, administered rectally (25 mg.kg-1 body wt) or intravenously (6 mg.kg-1) had arterial pH of 7.36 +/- 0.03 and PaCO2 of 40 +/- 4 mmHg. In 22 children over two years of age, the use of fentanyl (1.2 +/- 0.7 microgram.kg-1) in addition to the thiamylal did not change blood gas data compared to those children over two years receiving only barbiturates (pH 7.36 vs 7.36, PaCO2 41 vs 40 mmHg). Children with cyanotic congenital heart disease showed similar pH and PaCO2 to acyanotic children following administration of the short-acting barbiturate. Thiobarbiturates, given in a titrated fashion under direct observation, have clinically small effects on arterial pH and PaCO2 in paediatric patients.

Administration, Rectal↗

Effect of pH and PCO2 on pulmonary and systemic hemodynamics after surgery in children with congenital heart disease and pulmonary hypertension.

Fourteen children with congenital heart disease and associated pulmonary hypertension (preoperative mean pulmonary artery pressure (MPAP) 48 mm Hg +/- 1 SEM were examined to determine the effect of arterial carbon dioxide tension (PaCO2) and pH on pulmonary and systemic hemodynamics after surgical repair. Baseline measurements were obtained with hyperventilation to PaCO2 20 to 30 mm Hg (pH 7.56 +/- 0.01 mm Hg). The addition of carbon dioxide to inspired gas to achieve a PaCO2 40 to 45 mm Hg (pH 7.35 +/- 0.01) resulted in a significant increase in MPAP, from 32 +/- 5 mm Hg to 47 +/- 8 mm Hg (p less than 0.05). An increase in mean cardiac index (CI) from 2.7 +/- 0.3 L/min/m2 to 3.3 +/- 0.3 L/min/m2 (p less than 0.05) explained in part the associated increase in MPAP. For a subgroup of eight patients with postoperative MPAP greater than 30 mm Hg (at pH 7.35 to 7.40), pulmonary vascular resistance index (PVRI) also significantly increased (p less than 0.05) as PaCO2 was increased, implying a direct pulmonary vasodilating effect of alkalosis. Removal of carbon dioxide from inspired gas returned hemodynamic values to baseline. The higher the MPAP at physiologic pH the greater the absolute amount of MPAP reduction and PVRI reduction (p less than 0.05) with alkalosis. No complications from alkalosis were seen. We suggest that a trial of hypocarbic alkalosis in the child with severe residual pulmonary hypertension after surgical repair of congenital heart disease is warranted to reduce right ventricular afterload.

Adolescent↗