Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease.
(17/4441)
AIM: To evaluate the effects of low dose fentanyl infusion analgesia on behavioural and neuroendocrine stress response and short term outcome in premature infants ventilated for hyaline membrane disease. METHODS: Twenty seven ventilated preterm infants were randomly assigned to receive a mean fentanyl infusion of 1.1 (0.08 SE) micrograms/kg/h for 75 (5) hours, and 28 untreated infants were considered a control group. A behavioural sedation score was used to assess the infants' behaviour. Urinary metanephrine and the normetanephrine:creatinine molar ratio were determined at 0, 24, 48 and 72 hours. Outcome data and ventilatory indexes were recorded for each infant. RESULTS: The fentanyl group showed significantly lower behavioural stress scores and O2 desaturations than controls and lower urinary concentrations of metanephrine and normetanephrine at 24, 48, 72 hours. The two groups showed no significant difference in ventilatory variables or short term outcome. CONCLUSIONS: A short course of low dose fentanyl infusion reduces behavioural sedation scores, O2 desaturations and neuroendocrine stress response in preterm ventilated infants. (+info)
Effect of butorphanol tartrate on shock-related discomfort during internal atrial defibrillation.
(18/4441)
BACKGROUND: In patients with atrial fibrillation, intracardiac atrial defibrillation causes discomfort. An easily applicable, short-acting analgesic and anxiolytic drug would increase acceptability of this new treatment mode. METHODS AND RESULTS: In a double-blind, placebo-controlled manner, the effect of intranasal butorphanol, an opioid, was evaluated in 47 patients with the use of a step-up internal atrial defibrillation protocol (stage I). On request, additional butorphanol was administered and the step-up protocol continued (stage II). Thereafter, if necessary, patients were intravenously sedated (stage III). After each shock, the McGill Pain Questionnaire was used to obtain a sensory (S), affective (A), evaluative (E), and total (T) pain rating index (PRI) and a visual analogue scale analyzing pain (VAS-P) and fear (VAS-F). For every patient, the slope of each pain or fear parameter against the shock number was calculated and individual slopes were averaged for the placebo and butorphanol group. All patients were cardioverted at a mean threshold of 4.4+/-3.3 J. Comparing both patient groups for stage II, the mean slopes for PRI-T (P=0.0099), PRI-S (P=0.019), and PRI-E (P=0.015) became significantly lower in the butorphanol group than in the placebo group. Comparing patients who received the same shock intensity ending stage I and going to stage II, in those patients randomized to placebo the mean VAS-P (P=0.023), PRI-T (P=0. 029), PRI-S (P=0.030), and PRI-E (P=0.023) became significantly lower after butorphanol administration. CONCLUSIONS: During a step-up internal atrial defibrillation protocol, intranasal butorphanol decreased or stabilized the value of several pain variables and did not affect fear. Of the 3 qualitative components of pain, only the affective component was not influenced by butorphanol. The PRI evaluated pain more accurately than the VAS. (+info)
Opioidergic modulation of voltage-activated K+ currents in magnocellular neurons of the supraoptic nucleus in rat.
(19/4441)
Opioidergic modulation plays an important role in the control of oxytocin and vasopressin release by magnocellular neurons (MCNs) in the supraoptic and paraventricular nuclei of the hypothalamus. We have used whole cell patch-clamp recording in acute slices of the supraoptic nucleus (SON) of the hypothalamus to study opioidergic modulation of voltage-dependent K+ currents in MCNs that are involved in release activity. The mu-receptor agonist D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin (DAMGO, 2 microM) affected K+ currents in 55% of magnocellular neurons recorded from. In these putative oxytocinergic cells, DAMGO increased the delayed rectifier current (IK(V)) amplitude by approximately 50% without significant effects on its activation kinetics. The transient A current (IA) was enhanced by DAMGO by approximately 36%. Its inactivation kinetic was accelerated slightly while the voltage dependence of steady-state inactivation was shifted by -6 mV to more negative potentials. All DAMGO effects were blocked by the preferential non-kappa-opioid antagonist naloxone (10 microM). The kappa-opioid agonist trans-(+/-)-3, 4-dichloro-N-methyl-N(2-[1-pyrrolidinyl]cyclohexyl)benzeneacetamide (U50,488; 10 microM) strongly suppressed IK(V) by approximately 57% and evoked a 20-mV hyperpolarizing shift and an acceleration of activation in both, DAMGO-sensitive and -insensitive putative vasopressinergic MCNs. U50,488 reduced IA by approximately 29% and tau of inactivation by -20% in DAMGO-sensitive cells. In contrast, in DAMGO-insensitive cells U50,488 increased IA by approximately 23% and strongly accelerated inactivation (tau -44%). The effects of U50,488 were suppressed by the selective kappa-receptor antagonist nor-binaltorphimine (5 microM). We conclude that mu- and kappa-opioidergic inputs decrease and increase excitability of oxytocinergic MCNs, respectively, through modulation of voltage-dependent K+ currents. In vasopressinergic MCNs, kappa-opioidergic inputs differentially modulate these K+ currents. The modulation of K+ currents is assumed to significantly contribute to opioidergic control of hormone release by MCNs within the supraoptic nucleus and from the axon terminals in the neural lobe. (+info)
Comparison of adenosine and remifentanil infusions as adjuvants to desflurane anesthesia.
(20/4441)
BACKGROUND: Because adenosine has been alleged to produce both anesthetic and analgesic sparing effects, a randomized, double-blinded study was designed to compare the perioperative effects of adenosine and remifentanil when administered as intravenous adjuvants during general anesthesia for major gynecologic procedures. METHODS: Thirty-two women were assigned randomly to one of two drug treatment groups. After premedication with 0.04 mg/kg intravenous midazolam, anesthesia was induced with 2 micro/kg intravenous fentanyl, 1.5 mg/kg intravenous propofol, and 0.6 mg/kg intravenous rocuronium, and maintained with desflurane, 2%, and nitrous oxide, 65%, in oxygen. Before skin incision, an infusion of either remifentanil (0.02 microg x kg(-1) x min(-1)) or adenosine (25 microg x kg(-1) x min(-1)) was started and subsequently titrated to maintain systolic blood pressure, heart rate, or both within 10-15% of the preincision values. RESULTS: Adenosine and remifentanil infusions were effective anesthetic adjuvants during lower abdominal surgery. Use of adenosine (mean +/- SEM, 166+/-17 microg x kg(-1) x min(-1)) was associated with a significantly greater decrease in systolic blood pressure and higher heart rate values compared with remifentanil (mean +/- SEM, 0.2+/-0.03 microg kg(-1) x min(-1)). Total postoperative opioid analgesic use was 45% and 27% lower in the adenosine group at 0-2 h and 2-24 h after surgery, respectively. CONCLUSIONS: Adjunctive use of a variable-rate infusion of adenosine during desflurane-nitrous oxide anesthesia was associated with acceptable hemodynamic stability during the intraoperative period. Compared with remifentanil, intraoperative use of adenosine was associated with a decreased requirement for opioid analgesics during the first 24 h after operation. (+info)
Effects of prophylactic nalmefene on the incidence of morphine-related side effects in patients receiving intravenous patient-controlled analgesia.
(21/4441)
BACKGROUND: Opioid-related side effects associated with intravenous patient-controlled analgesia can be reduced by a low-dose naloxone infusion. The influence of nalmefene, a pure opioid antagonist with a longer duration of action, on opioid-related side effects has not been evaluated. This study was designed to determine the dose-response relation for nalmefene for the prevention of morphine-related side effects in patients receiving intravenous patient-controlled analgesia. METHODS: One hundred twenty women undergoing lower abdominal surgery were enrolled in the study. General anesthesia was induced using thiopental and rocuronium and maintained with desflurane, nitrous oxide, and fentanyl or sufentanil. All patients received neostigmine and glycopyrrolate to reverse residual neuromuscular blockade. No prophylactic antiemetics were administered. At the end of surgery, patients were randomized to receive saline, 15 microg nalmefene, or 25 microg nalmefene intravenously. The need for antiemetic and antipruritic drugs and the total consumption of morphine during the 24-h study were recorded. The incidences of postoperative nausea, vomiting, pruritus, and pain were recorded 30 min after patients were admitted to the postanesthesia care unit. In addition, patient remembrance of these side effects was noted at 24 h after operation. RESULTS: The need for antiemetic and antipruritic medications during the 24-h study period was significantly lower in the patients receiving nahmefene compared with those receiving placebo. However, the need to treat side effects was similar in the two nahmefene groups. Prophylactic administration of nalmefene reduced the patients remembrance of nausea and itching as assessed 24 h after operation. Although the total consumption of morphine during the 24-h study period was similar in the three groups, retrospectively patients who received nalmefene characterized their pain as less severe in the previous 24 h. CONCLUSION: Compared with placebo, prophylactic administration of nalmefene significantly decreased the need for antiemetics and antipruritic medications in patients receiving intravenous patient-controlled analgesia with morphine. (+info)
Pharmacokinetic modeling of M6G formation after oral administration of morphine in healthy volunteers.
(22/4441)
BACKGROUND: Morphine is metabolized to two major metabolites, morphine-3-glucuronide and morphine-6-glucuronide (M6G). Under the conditions of long-term oral morphine administration, the accumulation of M6G may contribute to the analgesic effects, but it may also cause respiratory depression. METHODS: Five healthy male volunteers (ages 25-34 yr) received 90 mg MST (morphine sulfate 5H2O sustained-released tablet, equivalent to 67.8 mg oral morphine). Multiple plasma and urine samples were taken for as long as 14 and 36 h, respectively. Individual pharmacokinetics after intravenous administration of morphine and M6G were available from a previous investigation. A new model that considers the M6G-plasma profile as a sum of the input from the first-pass metabolism of morphine and the input from systemically available morphine was applied to the plasma concentration versus time curves of M6G. The concentrations of M6G at the effect site after long-term morphine administration were simulated. RESULTS: The fraction of morphine absorbed from the gut was 82+/-14%. Of this, 42+/-8% passed through the liver, resulting in an oral bioavailability of morphine of 34+/-9%. Of the total amount of M6G, 71+/-7% was formed during the first-pass metabolism, and 29+/-7% was formed by metabolism of systemic morphine. After 36 h, the amounts of M6G and morphine excreted in the urine were 92+/-17% and 9+/-3%, respectively. Simulation of effect-site concentrations of M6G indicated that after multiple oral dosing of morphine in patients with normal liver and renal function, M6G might reach concentrations two times greater than that of morphine. CONCLUSIONS: M6G may contribute to the analgesic and side effects seen with long-term morphine treatment. The current model of morphine and M6G pharmacokinetics after oral administration of morphine may serve as a pharmacokinetic basis for experiments evaluating the analgesic contribution of M6G with long-term oral dosing of morphine. (+info)
Fentanyl and morphine, but not remifentanil, inhibit acetylcholine release in pontine regions modulating arousal.
(23/4441)
BACKGROUND: Opioids inhibit the rapid eye movement (REM) phase of sleep and decrease acetylcholine (ACh) release in medial pontine reticular formation (mPRF) regions contributing to REM sleep generation. It is not known whether opioids decrease ACh release by acting on cholinergic cell bodies or on cholinergic axon terminals. This study used in vivo microdialysis to test the hypothesis that opioids decrease ACh levels at cholinergic neurons in the laterodorsal tegmental nuclei (LDT) and LDT axon terminals in the mPRF. METHODS: Nine male cats were anesthetized with halothane, and ACh levels within the mPRF or LDT were assayed using microdialysis and high-pressure liquid chromatography (HPLC). ACh levels were analyzed in response to dialysis of the mPRF and LDT with Ringer's solution (control), followed by dialysis with Ringer's solution containing morphine sulfate (MSO4) or naloxone. ACh in the mPRF also was measured during either dialysis delivery or intravenous infusion of remifentanil and during dialysis delivery of fentanyl. RESULTS: Compared with dialysis of Ringer's solution, microdialysis with MSO4 decreased ACh by 23% in the mPRF and by 30% in the LDT. This significant decrease in ACh was antagonized by naloxone. MSO4 and fentanyl each caused a dose-dependent decrease in mPRF ACh when delivered by dialysis. Remifentanil delivered by continuous intravenous infusion or by dialysis into the mPRF did not alter mPRF ACh. CONCLUSIONS: Morphine inhibits ACh at the cholinergic cell body region (LDT) and the terminal field in the mPRF. ACh in the mPRF was not altered by remifentanil and was significantly decreased by fentanyl. Thus, MSO4 and fentanyl disrupt cholinergic neurotransmission in the LDT-mPRF network known to modulate REM sleep and cortical electroencephalographic activation. These data are consistent with the possibility that inhibition of pontine cholinergic neurotransmission contributes to arousal state disruption by opioids. (+info)
Effect of systemic morphine on the responses of convergent neurons to noxious heat stimuli applied over graded surface areas.
(24/4441)
BACKGROUND: Stimulus intensity is a major determinant of the antinociceptive activity of opiates. This study focused on the influence of the spatial characteristics of nociceptive stimuli, on opiate-induced depressions of nociceptive transmission at the level of the spinal cord. METHODS: Anesthetized rats were prepared to allow extracellular recordings to be made from convergent neurons in the lumbar dorsal horn. The effects of systemic morphine (1 and 10 mg/kg) were compared with those of saline for thermal stimuli of constant intensity, applied to the area of skin surrounding the excitatory receptive field (1.9 cm2) or to a much larger adjacent area (18 cm2). RESULTS: The responses (mean +/- SD) elicited by the 1.9-cm2 stimulus were not modified by 1 mg/kg intravenous morphine, although they were decreased by the 10-mg/kg dose (to 11+/-4% of control values compared with saline; P < 0.05). In contrast, when the 18-cm2 stimulus was applied, 1 mg/kg intravenous morphine produced a paradoxical facilitation of the neuronal responses (159+/-36% of control values; P < 0.05) and 10 mg/kg intravenous morphine resulted in a weaker depression of the responses (to 42+/-24% of control values; P < 0.05) than was observed with the smaller stimulus. CONCLUSIONS: Doses of systemic morphine in the analgesic range for rats had dual effects on nociceptive transmission at the level of the spinal cord, depending on the surface area that was stimulated. Such effects are difficult to explain in terms of accepted pharmacodynamic concepts and may reflect an opioid-induced depression of descending inhibitory influences triggered by spatial summation. (+info)