Lok-Hi Chow

Gender and pain upon movement are associated with the requirements for postoperative patient-controlled iv analgesia: a prospective survey of 2,298 Chinese patients.

PurposeTo investigate prospectively the influence of patient characteristics upon, and the association of postoperative measurements with, the requirements for postoperative morphine and the assessment of resting pain and pain upon movement in Chinese patients.MethodsFrom January 1998 to December 1999, patients receiving patient-controllediv morphine subsequent to general anesthesia and surgery at our institute (Kaohsiung Veterans General Hospital), were enrolled in the study. Demographic data (such as gender, age, weight, height and education level) and postoperative measurements, including pain scores at rest or during movement, sedation scores and morphine consumption, were recorded.ResultsIn total 2,298 patients were recruited. Females consumed significantly less morphine via patient-controlled analgesia (PCA) in the first three postoperative days than was the case for males (P < 0.05). Gender was the strongest predictor for postoperative morphine requirements. Postoperative pain upon movement was another effective predictor for morphine requirement (P < 0.05). Age, body height, body weight, education and operation sites were not associated with morphine consumption.ConclusionGender and postoperative pain upon movement are the major factors influencing morphine requirement for patientcontrollediv morphine analgesia during the first three postoperative days in Chinese patients.RésuméObjectifExaminer prospectivement si les caractéristiques du patient, et l’association des mesures postopératoires des douleurs, influencent les besoins de morphine postopératoire et l’évaluation de la douleur au repos et lors de mouvement chez des malades chinois.MéthodeDe janvier 1998 à décembre 1999, les patients qui ont reçu de la morphine iv auto-contrôlée, à la suite d’une opération sous anesthésie générale au Kaohsiung Veterans General Hospital, ont participé à l’étude. Les données démographiques (sexe, âge, poids, taille et niveau d’instruction) et les mesures postopératoires, incluant les scores de douleur au repos et pendant le mouvement, les scores de sédation et la consommation de morphine, ont été enregistrées.RésultatsNous avons recruté 2 298 patients. Pendant les trois premiers jours postopératoires, les femmes ont utilisé significativement moins de morphine que les hommes (P < 0,05) au moyen de l’analgésie auto-contrôlée (AAC). La variable prédictive la plus significative de la consommation de morphine postopératoire a été le sexe du patient. La douleur postopératoire pendant le mouvement a été un autre prédicteur efficace (P < 0,05). L’âge, la taille, le poids, l’instruction et le type d’opération n’ont pas été significatifs pour la consommation de morphine.ConclusionLe sexe et la douleur postopératoire pendant le mouvement sont les principaux facteurs d’influence des besoins de morphine pour l’analgésie iv auto-contrôlée pendant les trois premiers jours postopératoires chez des sujets chinois.

The preoperative administration of intravenous dextromethorphan reduces postoperative morphine consumption.

UNLABELLED We evaluated the effect of dextromethorphan on postoperative pain management. Sixty ASA physical status I-III female patients undergoing major abdominal surgery underwent standardized general anesthesia. Thirty patients received an i.v. infusion of dextromethorphan 5 mg/kg before anesthetic induction (Pre group), whereas the remaining 30 patients received the same volume of isotonic sodium chloride solution, followed by a postoperative i.v. infusion of dextromethorphan 5 mg/kg (Post group). Patients in the Pre group received the same volume of isotonic sodium chloride solution postoperatively. All patients were then treated with patient-controlled i.v. analgesia, which administered a 0.6-mg bolus of morphine on demand (maximal 4 h dose 20 mg). The mean visual analog pain score during cough or movement and at rest were similar in the two groups in the first 3 days postoperatively. However, Post group patients consumed more morphine than Pre group patients during the first 2 days (P < 0.01). The sedation scores, patient satisfaction, and the incidence of morphine-related side effects were similar between the two groups. We conclude that the preoperative administration of dextromethorphan 5 mg/kg reduces postoperative morphine consumption compared with postoperative administration. IMPLICATIONS In this double-blinded study, we found that the preoperative administration of i.v. dextromethorphan 5 mg/kg, compared with postoperative administration, reduces postoperative morphine consumption, which may provide clinical evidence of preemptive or preventive analgesic effects of dextromethorphan.

Effect of Oral Clonidine Premedication on Perioperative Hemodynamic Response and Postoperative Analgesic Requirement for Patients Undergoing Laparoscopic Cholecystectomy

BACKGROUND To investigate the clinical efficacy of oral clonidine premedication in anesthesia and analgesia in patients undergoing laparoscopic cholecystectomy (LC). METHODS One hundred and ten patients, scheduled for elective laparoscopic cholecystectomy, were recruited for the prospective, randomized, single-blind, comparative study. They were randomly allotted to either of the placebo or clonidine group. Patients of the placebo group (n = 65) were premedicated with oral antacid (alugel hydroxide 300 mg), while those in the clonidine group (n = 45) were premedicated with oral clonidine 150 micrograms prior to anesthesia. The premedication was given 60 to 90 min before the anticipated time of induction of anesthesia. Normocapnia was maintained throughout the perioperative period. Mass spectrometer was used to assess the inspired and expiratory concentrations of isoflurane, the anesthetic used for maintenance of anesthesia. Postoperative pain intensity, sedation scores, adverse events, time to the first dose of postoperative analgesic and cumulative analgesic requirement in 24 hours were recorded. Data were expressed as mean +/- SD. RESULTS Patients in the clonidine group displayed greater hemodynamic stability perioperatively and the isoflurane requirement was also reduced (30% less). The postoperative analgesic requirement was less (1.5 +/- 1.3 vs. 2.2 +/- 1.3 dose, P < 0.05) and the time for the first dose of analgesic was prolonged (411 +/- 565 vs. 264 +/- 441 min) in comparison with the placebo group but no statistic difference was found. CONCLUSIONS Oral clonidine premedication helped to provide perioperative hemodynamic stability, spared the use of isoflurane and reduced the requirement of postoperative analgesia so as to smoother the way to recovery in patients undergoing LC.

Dextromethorphan potentiates morphine antinociception at the spinal level in rats.

PurposeMorphine is an effective analgesic, but adverse effects limit its clinical use in higher doses. The non-opioid antitussive, dextromethorphan (DM), can potentiate the analgesic effect of morphine and decrease the dose of morphine in acute postoperative pain, but the underlying mechanism remains unclear. We previously observed that DM increases the serum concentration of morphine in rats. Therefore, we investigated the effects of drugs administered at the spinal level to exclude possible pharmacokinetic interactions. As DM has widespread binding sites in the central nervous system [such as N-methyl-D-aspartate (NMDA) receptors, sigma receptors and α3ß4 nicotinic receptors], we investigated whether the potentiation of morphine antinociception by DM at the spinal level is related to NMDA receptors.MethodsWe used MK-801 as atool to block the NMDA channel first, and then studied the interaction between intrathecal (i.t.) morphine and DM. The tail-flick test was used to examine the antinociceptive effects of different combinations of morphine and other drugs in rats.ResultsDM (2–20 μg) or MK-801 (5–15 μg) showed no significant antinociceptive effect by themselves. The antinociceptive effect of morphine (0.5 μg, i.t.) was significantly enhanced by DM and reached the maximal potentiation (43.7%–50.4%) at doses of 2 to 10 μg. Pretreatment with MK-801 (5 or 10μg, i.t.) significantly potentiated morphine antinociception by 49.9% or 38.7%, respectively. When rats were pretreated with MK-801, DM could not further enhance morphine antinociception (45.7%vs 50.5% and 43.3%).ConclusionOur results suggest that spinal NMDA receptors play an important role in the effect of DM to potentiate morphine antinociception.RésuméObjectifAnalgésique efficace, la morphine a cependant des effets indésirables qui en limite l’usage clinique à fortes doses. L’antitussif, dextrométhorphane (DM), peut augmenter l’effet analgésique de la morphine et permettre d’en utiliser une dose postopératoire plus faible, mais le mécanisme responsable de cette action est encore inconnu. Nous savons que le DM augmente la concentration sérique de la morphine chez les rats. Nous avons donc voulu explorer les effets de médicaments administrés au niveau rachidien afin d’exclure des interactions pharmacocinétiques possibles. Les sites de fixation du DM étant nombreux dans le système nerveux central [comme les récepteurs N-méthyl-D-aspartate (NMDA), les récepteurs sigma et les récepteurs nicotiniques α3ß4], nous avons vérifié si la potentialisation de l’antinociception de la morphine par le DM au niveau rachidien est reliée aux récepteurs NMDA.MéthodeNous avons utilisé le MK-801 pour bloquer d’abord le canal NMDA et étudier ensuite l’interaction entre la morphine intrathécale (i.t.) et le DM. Le test de latence de rétraction de la queue a été utilisé pour vérifier les effets antinociceptifs de différentes combinaisons de morphine et d’autres médicaments chez les rats.RésultatsLe DM (2– 20 μg) ou le MK-801 (5– 15 μg) n’ont montré aucun effet antinociceptif significatif par euxmêmes. L’effet antinociceptif de la morphine (0,5 μg, i.t.) a été significativement accru par le DM et a atteint sa potentialisation maximale (43,7 % –50,4 %) aux doses de 2 à 10 μg. Un prétraitement avec MK-801 (5 ou 10 μg, i.t.) a significativement augmenté l’effet antinociceptif de la morphine de 49,9% ou de 38,7 %, respectivement. Chez les rats prétraités avec MK-801, le DM ne pouvait augmenter davantage l’antinociception de la morphine (45,7% vs 50,5% et 43,3%). Conclusion : Nos résultats indiquent que les récepteurs NMDA jouent un rôle important dans l’effet de potentialisation de l’antinociception de la morphine par le DM.

Dextromethorphan differentially affects opioid antinociception in rats

1 Opioid drugs such as morphine and meperidine are widely used in clinical pain management, although they can cause some adverse effects. A number of studies indicate that N‐methyl‐D‐aspartate (NMDA) receptors may play a role in the mechanism of morphine analgesia, tolerance and dependence. Being an antitussive with NMDA antagonist properties, dextromethorphan (DM) may have some therapeutic benefits when coadministered with morphine. In the present study, we investigated the effects of DM on the antinociceptive effects of different opioids. We also investigated the possible pharmacokinetic mechanisms involved. 2 The antinociceptive effects of the μ‐opioid receptor agonists morphine (5 mg kg−1, s.c.), meperidine (25 mg kg−1, s.c.) and codeine (25 mg kg−1, s.c.), and the κ‐opioid agonists nalbuphine (8 mg kg−1, s.c.) and U‐50,488H (20 mg kg−1, s.c.) were studied using the tail‐flick test in male Sprague–Dawley rats. Coadministration of DM (20 mg kg−1, i.p.) with these opioids was also performed and investigated. 3 The pharmacokinetic effects of DM on morphine and codeine were examined, and the free concentration of morphine or codeine in serum was determined by HPLC. 4 It was found that DM potentiated the antinociceptive effects of some μ‐opioid agonists but not codeine or κ‐opioid agonists in rats. DM potentiated morphines antinociceptive effect, and acutely increased the serum concentration of morphine. In contrast, DM attenuated the antinociceptive effect of codeine and decreased the serum concentration of its active metabolite (morphine). 5 The pharmacokinetic interactions between DM and opioids may partially explain the differential effects of DM on the antinociception caused by opioids.

Dextromethorphan potentiates morphine-induced antinociception at both spinal and supraspinal sites but is not related to the descending serotoninergic or adrenergic pathways

Morphine is a strong and widely used opioid analgesic in pain management, but some adverse effects limit its clinical use at high doses. The clinically available non-opioid antitussive, dextromethorphan (DM) can potentiate the analgesic effect of morphine and decrease the dose of morphine in acute postoperative pain. However, the mechanism underlying this synergistic phenomenon is still not clear. To examine if the potentiation by DM occurs through the descending pain-inhibitory pathways, ketanserin (a 5-HT2 receptor antagonist) and yohimbine (an alpha2-adrenergic receptor antagonist) were employed and found to have no significant effect on the potentiation by DM. Using local delivery of drugs in rats in the present study, potentiation of morphine-induced antinociception by DM was observed via both intrathecal and intracerebroventricular routes, suggesting that both spinal and supraspinal sites are involved. This suggests that the potentiation of morphine-induced antinociception by DM is not mediated by the serotoninergic or adrenergic descending pain-inhibitory pathways. The present results are consistent with findings in clinical studies, which showed that DM can effectively decrease the consumption of morphine in patients suffering from pain. Since DM has excellent clinical potential as a synergistic agent with morphine, further investigating and clarifying the possible pharmacological mechanism of DM are of great importance for future studies.

Effects of morphine and endomorphins on the polysynaptic reflex in the isolated rat spinal cord

At the spinal level, μ-opioids exert their actions on nociceptive primary afferent neurons both pre- and postsynaptically. In the present study, we used an in vitro isolated neonatal rat (11–15 days old) spinal cord preparation to examine the effects of morphine and the endogenous μ-opioid ligands endomorphin-1 (EM-1) and endomorphin-2 (EM-2) on the polysynaptic reflex (PSR) of dorsal root-ventral root (DR-VR) reflex. The actions of μ-opioids on spinal nociception were investigated by quantification of the firing frequency and the mean amplitude of the PSR evoked by stimuli with 20×threshold intensity. EM-1 decreased the mean amplitude of PSR, whereas EM-2 and morphine decreased the firing frequency. The pattern of the effects elicited by morphine was the same as that for EM-2, except at high concentration. Naloxonazine, a selective μ1 opioid receptor antagonist, had no significant effect on PSR by itself, but blocked the inhibition of PSR firing frequency or amplitude induced by EM-1, -2 and morphine. This may suggest that EM-1, EM-2 and morphine modulate spinal nociception differently and act mainly at the μ1-opioid receptors. Although they all act via μ1-opioid receptors, their different effects on the PSR may suggest the existence of different subtypes of the μ1-opioid receptor. The present data is also consistent with a further hypothesis, namely, that morphine and EM-2 activate a subtype of μ1-opioid receptor presynaptically, while EM-1 acts mainly through another subtype postsynaptically. However, since other reports indicate that EM-2, but not EM-1, could stimulate the release of enkephalins or dynorphin, presynaptic δ and κ receptors may be also involved indirectly in the different regulation by μ-opioids at the spinal level.

Fatal gas embolism during transurethral incision of the bladder neck under spinal anesthesia.

UNLABELLED We report a case of fatal gas embolism during transurethral incision of the bladder neck under spinal anesthesia in a 76-yr-old man. We confirmed the diagnosis of venous gas embolism by aspiration of frothy blood through the double-lumen central venous catheter and by observation on the transesophageal echocardiogram of a massive gas embolism in the right atrium and right ventricle with obstruction of right ventricle outflow. This report is presented in an attempt to remind anesthesiologists of this unusual but potentially fatal complication that may occur during common transurethral surgery. IMPLICATIONS We report a patient undergoing transurethral incision of the bladder neck who developed a fatal gas embolism. This report is presented in an attempt to remind anesthesiologists of this unusual but potentially fatal complication that may occur during common transurethral surgery.

Successful anesthetic management of a patient with thyroid carcinoma invading the trachea with tracheal obstruction, scheduled for total thyroidectomy

We report a case of large thyroid carcinoma with tracheal and esophageal invasion who presented with preoperative stridor scheduled for total thyroidectomy and segmental tracheal resection. Careful and comprehensive preoperative anesthetic planning was done. Extracorporeal circulation membrane oxygenation (ECMO) was set up and running prior to induction under local anesthesia, due to an increased international normalized ratio (INR) and fear of bleeding in the airway. Fiberoptic bronchoscopy (FOB) is the first choice in many circumstances of difficult airway. However, we twice failed to intubate under FOB guidance. Successful intubation was done with traditional laryngoscopy and a Glidescope. The operative course was smooth. The oral endotracheal tube (ETT) was changed to a nasal ETT after surgery with the Glidescope. FOB-assisted intubation carries a chance of failure, and in critical patients, the presence of other intubating modalities such as video-assisted or fiberoptic-assisted technology or safety measures, including ECMO, will greatly increase the safety of anesthesia and surgery.

Sex Difference in Oxytocin-Induced Anti-Hyperalgesia at the Spinal Level in Rats with Intraplantar Carrageenan-Induced Inflammation.

Previously, we demonstrated intrathecal administration of oxytocin strongly induced anti-hyperalgesia in male rats. By using an oxytocin-receptor antagonist (atosiban), the descending oxytocinergic pathway was found to regulate inflammatory hyperalgesia in our previous study using male rats. The activity of this neural pathway is elevated during hyperalgesia, but whether this effect differs in a sex-dependent manner remains unknown. We conducted plantar tests on adult male and female virgin rats in which paw inflammation was induced using carrageenan. Exogenous (i.t.) application of oxytocin exerted no anti-hyperalgesic effect in female rats, except at an extremely high dose. Female rats exhibited similar extent of hyperalgesia to male rats did when the animals received the same dose of carrageenan. When atosiban was administered alone, the severity of hyperalgesia was not increased in female rats. Moreover, insulin-regulated aminopeptidase (IRAP) was expressed at higher levels in the spinal cords of female rats compared with those of male rats. Oxytocin-induced anti-hyperalgesia exhibits a sex-dependent difference in rats. This difference can partially result from the higher expression of IRAP in the spinal cords of female rats, because IRAP functions as an enzyme that degrades oxytocin. Our study confirms the existence of a sex difference in oxytocin-induced anti-hyperalgesia at the spinal level in rats.