Lack of analgesic effect of parecoxib following laparoscopic cholecystectomy.

BACKGROUND: The cyclo-oxygenase-2 inhibitor, parecoxib, can be administered parenterally. The recommended dose for post-operative use is 40 mg twice daily, which may not be the appropriate dose for the treatment of visceral pain. We studied the effect of a single dose of parecoxib of either 40 or 80 mg in laparoscopic cholecystectomy, and its effect on opioid-induced side-effects. METHODS: Seventy-three patients scheduled for elective laparoscopic cholecystectomy were enrolled in this prospective, randomized, double-blind study. Patients were randomized into three groups: a placebo-treated control group, a 40-mg parecoxib-treated group (P40) and an 80-mg parecoxib-treated group (P80). We recorded the cumulative fentanyl consumption during the first 20 h post-operatively by patient-controlled analgesia equipment, the pain scores during rest, coughing and mobilization (visual analogue scale, 0-10), the worst pain during the first 2 h post-operatively and in the following 18 h, and the side-effects by questionnaire. RESULTS: No significant differences in fentanyl consumption between the three groups could be detected. The worst pain experienced between 2 and 20 h post-operatively on the ward was significantly lower in the P80 group than in the control group. CONCLUSION: The recommended dose of parecoxib, 40 mg, is not effective for the treatment of pain during the early post-operative period after laparoscopic cholecystectomy. Doubling the dose to 80 mg seems to improve the results.

Laparoscopically assisted vaginal and abdominal hysterectomy: comparison of postoperative pain, fatigue and systemic response. A case-control study.

BACKGROUND AND OBJECTIVE: Laparoscopic and open surgery have been compared with conflicting results regarding their systemic responses. The sensitivity of biochemical markers that are used to discriminate between the stress responses to different types of surgery varies from study to study. We wanted to evaluate the stress response and the sensitivity of clinical and biochemical stress markers in patients undergoing laparoscopically assisted vaginal or abdominal hysterectomy. METHODS: We performed a case-control study with patients undergoing laparoscopically assisted vaginal hysterectomy (n=20) or abdominal hysterectomy (n=20). Pain scores were assessed at rest and during coughing, and active leg elevation and fatigue scores using a visual analogue scale. In 10 patients of each group, haematocrit, white cell count, C-reactive protein, glucose, cortisol, adrenocorticotrophic hormone, beta-endorphin immunoreactivity, interleukin-6 and urine excretion of epinephrine and norepinephrine were measured preoperatively and during the first 44 postoperative hours. RESULTS: The most sensitive symptoms and markers of the systemic response were pain scores during mobilization, fatigue scores, C-reactive protein and interleukin-6 (P < 0.01 in all comparisons). Pain scores at rest, and all other laboratory markers of the systemic response, did not discriminate between the two types of surgery. CONCLUSION: Follow-up of postoperative pain scores during mobilization and fatigue levels might be an easy tool for the evaluation of postoperative recovery. Using an identical anaesthetic technique, the neuroendocrine response was of the same magnitude after both types of surgery.

Potency of propofol, thiopentone and ketamine at various endpoints in New Zealand White rabbits.

Effective plasma concentrations of propofol, thiopentone and ketamine were determined at different endpoints in a study with randomized, crossover design in nine New Zealand White rabbits. A continuous infusion was used (30 ml/h) with concentrations of 10 mg/ml for propofol, 25 mg/ml for thiopentone and 20 mg/ml for ketamine. The endpoints were loss of the righting reflex, loss of purposeful reactions to tail clamping (as an example of a peripheral pain stimulus) or to intranostril insufflation of ammonia vapour (as an example of a central reflex stimulus), and the recovery of these reflexes and reactions. According to the ED50 values the potency ratios of propofol, thiopentone and ketamine were at the loss of righting reflex 1:1.8:1.2, at the loss of reaction to ammonia vapour 1:1.5:1.6, and at the loss of reaction to tail clamping 1:1.5:3.9, respectively. Recovery was significantly faster after propofol than after thiopentone and ketamine. Measuring the effective plasma concentrations of intravenous anaesthetics provides a method of relating dose to effect, but there still remains a variable gap between plasma concentration and effect.

Efficacy and safety of premedication with oral ketamine for day-case adenoidectomy compared with rectal diazepam/diclofenac and EMLA.

BACKGROUND: Because of its pain-attenuating and sedative properties oral ketamine has been used as premedication in children and adults. We wanted to compare in children scheduled for adenoidectomy safety and efficacy of oral ketamine with a premedication that causes similar preoperative sedation and relief of pain at the venepuncture site. We also evaluated the effect of i.v. glycopyrrolate added to these combinations. METHODS: One hundred children between 10 and 15 kg of body weight scheduled for day-case adenoidectomy were randomly assigned to one of four groups: groups DG and DS received diclofenac 12.5 mg and diazepam 0.5 mg/kg rectally, EMLA cream at the venepuncture site, and placebo orally; groups KG and KS received ketamine 6.0 mg/kg orally, placebo cream at the puncture site, and placebo rectally; additionally, groups DG and KG received glycopyrrolate 5 microg/kg, and groups DS and KS received placebo intravenously. We recorded perioperatively scores (open scale 1-9) for stridor, sedation, bleeding, nausea, pain, heart rate, the need for analgesics and registered psychotomimesis and well-being at home. RESULTS: The children of the K-groups became more tearful during separation from their parents (P=0.0072). No other differences were found between the ketamine and diazepam/diclofenac groups before and after premedication until induction of anaesthesia. Oral ketamine produced unpleasant psychotomimesis in four out of 59 children. During the first 10 min postoperatively, the score for stridor was significantly higher in group KS than in the D-groups; stridor scores > or = 6 were seen in one child of the D-groups (DS) and in six children of the K-groups (n.s.), of whom three developed laryngospasm (one reintubation). Glycopyrrolate diminished salivation in all groups, but had no effect on stridor scores. Additionally, glycopyrrolate delayed the onset of eating at home. CONCLUSION: Premedication with racemic oral ketamine 6 mg/kg does not seem to be suitable for upper airway procedures. Addition of i.v. glycopyrrolate before the induction of anaesthesia significantly reduced the scores for salivation.

Does monitoring of post-tetanic count prevent alarms of airway pressure or visible muscle activity during intratracheal jet ventilation? A prospective study with five different neuromuscular blocking agents.

OBJECTIVE: Profound neuromuscular block (NMB) quantified by post-tetanic count (PTC) may prevent all muscle activity during anesthesia. We studied whether monitoring of PTC prevents airway pressure alarms or visible movements of the vocal cords and the abdomen during endolaryngeal procedures (ELPs). METHODS: In this prospective, double blind, study 50 healthy (ASA 1-3) patients scheduled for ELPs were randomized into five groups: atracurium, mivacurium, rocuronium, vecuronium and succinylcholine. During alfentanil-propofol anaesthesia, profound NMB was controlled by monitoring the PTC (target level PTC 0-2, 50 Hz tetanic stimulation) of the adductor pollicis muscle. The muscle relaxants were administered using bolus dosing in all groups but in the succinylcholine group. The early signs of recovery of NMB to be observed were: 1) airway pressure alarms, 2) movements of vocal cords on the laryngeal video monitor and 3) movements of the abdomen. The inference was based on 90% confidence interval tests. RESULTS: During 50 ELP:s following signs of early recovery of NMB were recognized: 2 alarms of airway pressure, 16 laryngeal movements and 11 movements of the abdomen. The proportion of airway pressure alarms was significantly lower than proportion of all detectable movements (95% confidence interval analysis). Twelve of the movements were recorded at PTC zero level. The signs of early recovery of NMB were detected in all groups. CONCLUSIONS: PTC-monitoring following 50 Hz stimulation does not ensure total inactivity of muscles during alfentanil-propofol anesthesia, regardless which relaxant has been chosen. During ELPs, simultaneous observation of the vocal cords and the abdomen is more sensitive in detecting early recovery of NMB compared to our method of airway pressure monitoring.

The costs of intense neuromuscular block for anesthesia during endolaryngeal procedures due to waiting time.

UNLABELLED: The goal of this double-blinded, prospective study was to compare the costs incurred by waiting time of intense neuromuscular block while posttetanic count (PTC) was maintained at 0-2 during jet ventilation. Fifty patients were randomized into five groups to receive atracurium (ATR), mivacurium (MIV), rocuronium (ROC), vecuronium (VEC), and succinylcholine (SUCC). PTC < or =2 was maintained until completion of laryngomicroscopy by administering additional doses of relaxants or by adjusting the speed of the infusion of SUCC. We compared waiting time, i.e., onset time and recovery time, and costs of intense neuromuscular block. The expenses due to waiting time were calculated based on the average costs in the otorhinolaryngological operating room in Tampere University Hospital: FIM 40 (approximately $8) per minute in 1997. MIV and SUCC differ favorably from ATR, ROC, and VEC when waiting time and costs are concerned. The recovery times with MIV and SUCC were considerably shorter than those with ATR, ROC, and VEC (P < 0.001 in all pairwise comparisons). Using the muscle relaxant with the longest waiting time instead of that with the shortest waiting time (difference 21.8 min) cost more than FIM 800 (approximately $160) extra per patient. IMPLICATIONS: In this randomized, double-blinded, prospective study, we evaluated the costs of intense neuromuscular block due to waiting time. Succinylcholine and mivacurium are the most economical muscle relaxants to use when intense neuromuscular block is mandatory. Using intermediate-acting muscle relaxants results in unduly prolonged recovery time and extra costs.

Neuromuscular blocking characteristics of vecuronium after tubocurarine-induced "fade". An experimental double-blind clinical study.

OBJECTIVE: The fade in train-of-four (TOF) monitoring is considered to be due to blocking of the prejunctional nicotinic acetylcholine receptors (AchRs). During onset of the neuromuscular block (NMB) tubocurarine (TC) causes more fade in the TOF responses than vecuronium (VEC). Therefore we wanted to investigate whether onset or duration of action of VEC or TC would be improved with a priming dose of an agent with different prejunctional activity. METHODS: The rates of NMB were measured following priming doses of 0.15 mg x kg(-1) of TC and 0.015 mg x kg(-1) of VEC with 6 min priming time. The individual time course of action of 0.6 mg x kg(-1) of TC (1.13 x ED 95) and 0.1-0.2 mg x kg(-1) of VEC (1.75-3.5 x ED95) were examined with a priming dose of the same agent or the other agent, by measurement of changes in the evoked compound EMG from the hypothenar muscle. RESULTS: Priming doses of TC decreased mean TOF ratio to 67% [95% confidence interval (CI) = 56-78] during priming time, which was significantly lower than after priming with VEC 87% (76-97; P < 0.001). Despite the higher TOF ratio, the priming dose of VEC accelerated the onset time of intubation dose of TC more than the priming dose of TC (P = 0.0018). Priming with TC prolonged the duration of VEC-induced NMB by 35-70 min compared with priming with VEC, which means that a small priming dose of TC changes VEC from a muscle relaxant with intermediate action to a long-acting agent. CONCLUSION: Priming with TC caused a lower TOF ratio; however, priming with TC did not accelerate the onset time of either agent as much as priming with VEC. It appears that potentiation of NMB after combination of VEC and TC is not dependent on "fade" receptors.

Cortical responses to auditory stimuli during isoflurane burst suppression anaesthesia.

The cortical responses to auditory stimuli were studied in 12 patients during isoflurane anaesthesia producing burst suppression (ETisof (SD) 1.4 (0.2) vol.%). Earphones were used to give 3-s trains of auditory click stimuli (60 clicks, 20 clicks per second, 80 dB, 0.1 ms) at irregular intervals. In 10 patients, the electroencephalography (EEG) showed a burst suppression pattern consisting of high-amplitude activity intermingled with suppressed background activity. In eight patients with burst suppression patterns, there was a strong cortical reactivity to the termination, not to the beginning, of auditory stimuli: 80 (20)% of all stimuli presented during EEG suppression evoked high amplitude cortical response, offset-burst. The latency of these auditory offset evoked bursts was 540 (60) ms. Auditory offset evoked bursts suggest that in spite of cortical suppression during deep anaesthesia the brain retains its ability to respond to changes in the acoustic environment.

Does abstinence from smoking or a transdermal nicotine system influence atracurium-induced neuromuscular block?

UNLABELLED: The purpose of the present study was to investigate the interaction of chronic smoking and the actions of atracurium (ATR). Twenty nonsmokers (NON-SMOK) were compared with 80 smokers, who were randomized into three groups: 30 patients received 21 mg/d transdermal nicotine system > or = 10 h before fentanyl/thiopental/N2O/O2/isoflurane anesthesia (TD-NICO), whereas the abstinent group received a placebo transdermal system (ABST, n = 30). The TD-NICO and ABST groups refrained from smoking for at least 10 h before the induction of anesthesia. A third group was allowed to smoke until 1-3 h before anesthesia (SMOK, n = 20). Neuromuscular block was monitored using a Relaxograph (Datex, Helsinki, Finland). The electromyographic response was recorded from the first dorsal interosseus muscle of the hand. The inspiratory isoflurane concentration was kept constant at 0.7 vol% in all patients. After an initial bolus dose of 0.5 mg/kg ATR, no significant difference was observed among the groups regarding onset time and maximal neuromuscular block. In Group ABST, the duration of block until 25% recovery of T1 was 48.2 +/- 10.1 min, which was significantly longer (analysis of variance post hoc tests) than in Groups TD-NICO, SMOK, and NON-SMOK (42.7 +/- 7.1, 41.4 +/- 10.4, and 42.8 +/- 7.3 min, respectively). The maintenance dose of ATR in Group ABST (0.23 +/- 0.03 mg x kg(-1) x h(-1)) was smaller than in Groups TD-NICO, SMOK, and NON-SMOK (0.30 +/- 0.07, 0.32 +/- 0.06, and 0.32 +/- 0.05 mg x kg(-1) x h(-1), respectively). We conclude that abstinence from smoking increases the duration of ATR-induced neuromuscular block and reduces the maintenance dose of ATR in smokers. Perioperative use of a transdermal nicotine system prevents these abstinence-induced changes in duration and maintenance-dose. IMPLICATIONS: The purpose of the present study was to investigate the interaction of chronic smoking and atracurium. Smokers who refrain from smoking for > 10 h require a smaller maintenance dose of atracurium than nonsmokers. However, using a transdermal nicotine system prevents the decrease in maintenance dose during abstinence.

Edrophonium is better than neostigmine to antagonize residual vecuronium induced neuromuscular block.

Edrophonium (EDR) has the advantages of a quick onset of action and reduced cholinergic effects compared to neostigmine (NST) when they are used to antagonize neuromuscular block (NMB). There are few studies about antagonism of very weak residual NMB. Therefore we compared hemodynamic stability, train-of-four (TOF) characteristics and reversal time (time from administration of antagonists to train-of-four-ratio (TR) at least 0.70) of EDR 0.5 mg kg-1 + atropine (ATR) 0.007 mg kg-1 to NST 0.04 mg kg-1 + glycopyrrolate (GLY) 0.008 mg kg-1 when they were used to antagonize a residual vecuronium (VEC)-induced NMB (T1 25-75%). The NMB was monitored in 64 patients using the evoked electromyogram of the hypothenar muscle of the hand. An adequate antagonism was defined as a TR of 0.70 or higher. Heart rate was significantly higher in NST+GLY group 2 min after administration of the antagonists in comparison with the EDR+ATR group. The advantages of EDR (higher T1, TR and percentage of patients with an adequate recovery) were obvious during the first 5 min of reversal time. Therefore we conclude, that under the conditions described in the present study, EDR antagonizes residual VEC induced NMB faster than NST.

Effect of intravenous diclofenac or indomethacin on the emergence from anaesthesia for tonsillectomy.

We evaluated the effects of a single dose of diclofenac (75 mg) or indomethacin (50 mg) on intraoperative events and on the early recovery phase. The study was performed in a randomised, double-blind, placebo-controlled fashion in 63 adult patients scheduled for elective tonsillectomy. Study infusions started intravenously immediately after the induction of general anaesthesia with thiopentone; maintenance was with N2O/O2 and halothane. After intubation with the aid of suxamethonium, the patients breathed spontaneously via a Bain coaxial system. Perioperative events (bleeding tendency, bleeding, need for pain medication, physical recovery) were recorded with the aid of a questionnaire applied to the anaesthesia nurses and estimation of vigilance, attention, concentration, short-term memory, and simple motor speed during recovery was with the aid of three neuropsychological tests (thumb tapping test, digit span test and homogenic interference test). No significant differences between the three groups were found in systolic and diastolic arterial pressures, the results of the questionnaire, and those of the neuropsychological tests. The ability to keep the head elevated for at least 5 s recovered significantly later (P < 0.05) and heart rate levels in the indomethacin group were significantly lower (P < 0.001) than in the other two groups. No enhanced bleeding during the perioperative period was observed. Diclofenac and indomethacin in the doses used in our study have only a marginal effect on the patient's emergence from anaesthesia.

The effect of diclofenac and ketoprofen on halothane MAC in rabbit.

Non-steroidal anti-inflammatory drugs obviously act also on the central nervous system. We, therefore, studied the effect of diclofenac 3 mg/kg and ketoprofen 4 mg/kg on the minimum alveolar concentration (MAC) of halothane in 10 New Zealand White rabbits. After determination of halothane MAC, total doses of NSAIDs were administered intravenously as three subdoses: 12.5%, 37.5% and 50% of the total dose. Depth of anaesthesia did not increase significantly after the first two doses with either drug. With ketoprofen, halothane MAC increased after subdose 3 from 1.52 (SD 0.42) vol% to 1.9 (SD 0.36) vol% (p < 0.01). With diclofenac, halothane MAC increased after subdose 3 from 1.44 (SD 0.18) vol% to 1.60 (SD 0.39) vol% (ns). With both drugs, large interindividual differences of MAC appeared after full doses of NSAIDs.

Diclofenac and ketoprofen for pain treatment after elective caesarean section.

We have studied the effect of a constant infusion of diclofenac 150 mg/24 h, ketoprofen 200 mg/24 h or placebo on postoperative pain after elective Caesarean section performed under spinal or extradural block in 90 patients in a prospective, randomized and double-blind study. During the first 24 h after operation, patients in the treatment groups were more comfortable than the placebo group (P < 0.005); the diclofenac group needed a mean of oxycodone 21.6 mg/24 h and the ketoprofen group 21.2 mg/24 h, compared with 38.3 mg/24 in the placebo group (P < 0.001); the mean time to the first injection of oxycodone was 270.5 min in the diclofenac group, 270.2 min in the ketoprofen group and 161.2 min in the placebo group (P < 0.001). During the first 24 h after operation, the temperature increased in the control group by 0.7 degrees C compared with 0.1 degrees C in the diclofenac group and 0.3 degrees C in the ketoprofen group. One patient in the diclofenac group was eliminated from the study because of uterine relaxation during the first 30 min after start of the drug infusion; this improved after cessation of diclofenac and infusion of sulprostone. There were no other serious side effects.

The effect of paracetamol or diclofenac administered before operation on postoperative pain and behaviour after adenoidectomy in small children.

We compared the effects of rectally administered diclofenac (12.5 mg) with paracetamol (125 mg) on pre- and postoperative behaviour and the need for supplementary analgesia in 44 children scheduled for adenoidectomy (with or without myringotomy). The study drugs were given in combination with diazepam (0.5 mg.kg-1) about 20 min before the children were taken to the operating theatre. On arrival there, the children who had received diclofenac were significantly quieter (< 0.05), easier to handle (p < 0.01) and cried less (p < 0.05) than those in the paracetamol group. During recovery, children in the diclofenac group needed fewer supplementary doses of intravenous pethidine than those receiving paracetamol (p < 0.001). There were no obvious differences between the groups in intra-operative bleeding (as estimated by the surgeon), or in measured blood loss. No postoperative complications became evident. The pre-operative rectal administration of diclofenac for pain relief after adenotomy is safe and effective.

Effects of peri-operatively administered diclofenac and indomethacin on blood loss, bleeding time and plasma prostanoids in man.

Sixty-seven patients scheduled for gynaecological laparotomy were anaesthetized with enflurane and divided at random into three groups to investigate double blind the effects of diclofenac (21 pts), indomethacin (23 pts) and placebo (23 pts) on haemostasis. Of each group eight to ten patients were chosen at random for estimation of peri-operative concentrations of prostanoids in plasma (thromboxane B2, prostaglandin E2). The pre-operative loading dose was diclofenac 33.6 mg or indomethacin 25 mg, followed by infusion for 24 h of diclofenac 6.7 mg h-1 or indomethacin 5 mg h-1. A fourth group received balanced anaesthesia (21 pts) and served as an additional control group for estimation of bleeding tendency and blood loss. The groups matched statistically for duration of surgery, age, weight, and height. No significant differences were found for prostaglandin E2 values, operation time, intra-operative blood loss, bleeding time, and frequency of post-operative haematomas. The most frequent surgeons' complaint was of increased bleeding tendency with indomethacin (P less than 0.001). Thromboxane B2 values in plasma were increased 30 min (66%) and 24 h (30%) after beginning of surgery in the placebo group (P less than 0.025). Diclofenac and indomethacin totally abolished these increases. During infusion of the loading dose of indomethacin one patient developed bradyarrhythmia, which was easily treated. No other complications appeared.