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Biomedical subjects

A M Lynn

Publications and source records attributed to A M Lynn.

At least 19 recordsLinked to original sources
PubMed1997

Morphine pharmacokinetics during continuous infusion of morphine sulfate for infants receiving extracorporeal membrane oxygenation.

OBJECTIVES: To determine a) if serum morphine concentration changes during the first 3 hrs of extracorporeal membrane oxygenation (ECMO); and b) if absorption of morphine onto the membrane oxygenator is responsible for these changes. Also, morphine clearance during the first 5 days of ECMO was studied. DESIGN: Prospective, open-label study with consecutive patient enrollment. SETTING: Neonatal intensive care unit at a university-affiliated, children's hospital. SUBJECTS: Eleven neonates with severe persistent pulmonary hypertension of the newborn receiving continuous intravenous infusions of morphine sulfate and requiring ECMO. INTERVENTIONS: Blood samples were obtained from the subjects and ECMO circuits at predetermined time intervals. MEASUREMENTS AND MAIN RESULTS: Serum morphine concentration was determined using high-performance liquid chromatography. Morphine concentrations were no different from baseline at 5 mins, 1 hr, or 3 hrs after beginning ECMO. There was no significant difference in morphine concentration from samples taken immediately proximal and distal to the membrane oxygenator at 5 mins, 1 hr, and 3 hrs after the start of ECMO. Morphine clearance was calculated on days 1, 3, and 5 of ECMO. The mean value for morphine clearance was 11.7 +/- 9.3 (SD) ml/min/kg (range 2.6 to 34.5). CONCLUSIONS: The initiation of ECMO does not lead to a significant decrease in serum morphine concentration and there is no uptake of morphine onto the membrane oxygenator of the ECMO circuit. Morphine clearance for infants receiving ECMO is variable.

Chromatography, High Pressure Liquid↗
PubMed1996

Epidural and intravenous bolus morphine for postoperative analgesia in infants.

PURPOSE: To compare two doses of bolus epidural morphine with bolus iv morphine for postoperative pain after abdominal or genitourinary surgery in infants. METHODS: Eighteen infants were randomly assigned to bolus epidural morphine (0.025 mg.kg-1 or 0.050 mg.kg-1) or bolus iv morphine (0.050-0.150 mg.kg-1). Postoperative pain was assessed and analgesia provided, using a modified infant pain scale. Monitoring included continuous ECG, pulse oximetry, impedance and nasal thermistor pneumography. The CO2 response curves and serum morphine concentrations were measured postoperatively. RESULTS: Postoperative analgesia was provided within five minutes by all treatment methods. Epidural groups required fewer morphine doses (3.8 +/- 0.8 for low dose [LE], 3.5 +/- 0.8 for high dose epidural [HE] vs. 6.7 +/- 1.6 for iv, P < 0.05) and less total morphine (0.11 +/- 0.04 mg.kg-1 for LE, 0.16 +/- 0.04 for HE vs 0.67 +/- 0.34 for iv, P < 0.05) on POD1. Dose changes were necessary in all groups for satisfactory pain scores. Pruritus, apnoea, and haemoglobin desaturation occurred in all groups. CO2 response curve slopes, similar preoperatively (range 36-41 ml.min-1.mmHg ETCO2-1.kg-1) were generally depressed (range, 16-27 ml.min-1.mmHg ETCO2-1.kg-1) on POD1. Serum morphine concentrations, negligible in LE (< 2 ng.ml-1), were similar in the HE and iv groups (peak 8.5 +/- 12.5 and 8.6 +/- 2.4 ng.ml-1, respectively). CONCLUSION: Epidural and iv morphine provide infants effective postoperative analgesia, although side effects are common. Epidural morphine gives satisfactory analgesia with fewer doses (less total morphine); epidural morphine 0.025 mg.kg-1 is appropriate initially. Infants receiving epidural or iv morphine analgesia postoperatively need close observation in hospital with continuous pulse oximetry.

Analgesia, Epidural↗
PubMed1996

Comparison of hetastarch with albumin for postoperative volume expansion in children after cardiopulmonary bypass.

OBJECTIVE: Hetastarch has been studied as a volume expander in adults after cardiopulmonary bypass (CPB) and in recommended dosages has not altered coagulation studies or increased clinical bleeding. Hetastarch was compared with albumin in children after CPB to determine whether hetastarch use was associated with increased clinical bleeding or alteration of coagulation studies. DESIGN: Randomized double-blinded study. SETTING: University-affiliated children's hospital. PARTICIPANTS: Forty-seven children age 1 year or greater (mean 72.8 months; range 12 months to 15.5 years) scheduled for repair of congenital heart disease with moderate hypothermia were randomized to receive hetastarch or albumin as a postoperative volume expander during the first 24 hours after surgery. INTERVENTIONS: Thirty-eight children required colloid replacement therapy. Blood pressure, central venous pressure, urine output, and chest tube drainage were used to determine colloid requirement. MEASUREMENTS AND MAIN RESULTS: Clinical bleeding and laboratory studies of coagulation were evaluated as were requirements for colloid, crystalloid, and blood products. Twenty children received 6% hetastarch, and 18 received 5% albumin. No differences were found in the amount of replacement fluids required, or in coagulation parameters in children receiving 20 mL/kg or less of either colloid replacement therapy. An increase in prothrombin time was demonstrated in children who received greater than 20 mL/kg of 6% hetastarch (p = 0.006); however, no difference in clinical bleeding or blood product requirement was demonstrated between the hetastarch or albumin groups receiving more than 20 mL/kg. CONCLUSION: This study demonstrated that 6% hetastarch is safe and an effective plasma volume expander in the postoperative management of children, using volumes up to 20 mL/kg. Close laboratory monitoring and careful evaluation of clinical bleeding are suggested when larger doses of hetastarch are administered because of prolongation of the prothrombin time with more than 20 mL/kg of hetastarch.

Adolescent↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1993

Towards 2000.

Explore the source record for details and available documents.

Dental Auxiliaries↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗