Different priming techniques,including mivacurium,accelerate the onset of rocuronium

Different priming sequences of equipotent doses of rocuronium and mivacurium on the onset of maximum neuromuscular block and intubating conditions were compared with those obtained after succinylcholine. During thiopentone-fentanylnitrous oxide anaesthesia, 70 patients were randomly assigned into seven groups. Group I received mivacurium 0.15 mg · kg^?1 as a single bolus dose. Group II received a priming dose of mivacurium 0.015 mg · kg^?1 followed three minutes later by mivacurium 0.135 mg · kg^?1. Group III received rocuronium 0.6 mg · kg^?1 as a single bolus dose, and Group IV received an initial dose of rocuronium 0.06 mg · kg^?1 followed by rocuronium 0.54 mg · kg^?1. Group V received a priming dose of mivacurium 0.015 mg · kg^?1 followed by rocuronium 0.54 mg · kg^?1. Group VI received an initial dose of rocuronium 0.06 mg · kg^?1 followed by mivacurium 0.135 mg · kg^?1. Group VII received succinykholine 1.0 mg · kg^?1. Groups I, III, and VII received a placebo injection before the administration of the neuromuscular blocking drug. Additional thiopentone 2 mg · kg^?1 iv was given 30 sec before intubation. Onset times (mean (95% confidence interval)) after priming a rocuronium block with either rocuronium (73 (57–90) sec) or mivacurium (58 (47–69) sec) were similar to those after succinykholine (54 (40–68) sec), and were shorter (P < 0.01) than that observed in other groups. Intubating conditions were not different between the groups. The duration of neuromuscular block was shortest with succinykholine. It is concluded that priming a rocuronium block with either mivacurium or rocuronium resulted in a neuromuscular block comparable to that of succinykholine in both the onset of action and intubating conditions.     

Edrophonium antagonism of vecuronium at varying degrees of fourth twitch recovery

The purpose of this study was to determine the optimal dose of edrophonium needed for successful antagonism (train-of-four ratio, or T₄/T₁ > 0.7) of vecuronium-induced blockade when all four twitches were visible in response to indirect train-offour (TOF) stimulation. Forty patients, scheduled for elective surgical procedures not exceeding 120 min, received vecuronium, 0.08 mg · kg^?1, during thiopentone-N₂O-isoflurane anaesthesia. Train-of-four stimulation was applied every 20 sec and the force of contraction of the adductor pollicis muscle was recorded. Increments of vecuronium, 0.015 mg · kg^?1, were given as required. At the end of surgery, and provided that neuro-muscular activity had recovered to four visible twitches, edrophonium, 0.1 mg · kg^?1, was given. Two minutes later, edrophonium, 0.1 mg · kg^?1, was given if T₄/T₁ did not reach 0.7. After another two minutes, edrophonium, 0.2 mg · kg^?1, was given if T₄/T₁ did not reach 0.7 or more. Finally, if T₄/ T₁ was still < 0.7, a dose of 0.4 mg · kg^?1 was given. Seventeen patients (42.5%) required 0.1 mg · kg^?1 of edrophonium for successful reversal, sixteen patients (40%) needed a cumulative dose of 0.2 mg · kg^?1 and six patients (15%) required 0.4 mg · kg^?1. Only one patient received 0.8 mg · kg^?1. There was a good correlation between T₄/ T₁ two minutes after the first dose of edrophonium and pre-reversal T₄/T₁ (r = 0.6; P = 0.00014). All patients with pre-reversal T₄/ T₁ > 0.23 required at most 0.2 mg · kg^?1 of edrophonium for successful reversal. We conclude that when all four twitches are clearly visible following train-of-four stimulation, small doses of edrophonium (0.1-0.2 mg · kg^?1) might be sufficient to antagonize vecuronium neuromuscular blockade.     

Regional anaesthesia for hernia repair in children: local vs caudal anaesthesia

The purpose of this study was to compare the effect of local anaesthesia (LA) with that of caudal anaesthesia (CA) on postoperative care of children undergoing inguinal hernia repair. This was a randomized, single-blind investigation of 202 children aged 1–13 yr. Anaesthesia was induced with N₂O/O₂ and halothane or propofol and maintained with N₂O/O₂/halothane. Local anaesthesia included ilioinguinal and iliohypogastric nerve block plus subcutaneous injection by the surgeon of up to 0.3 ml · kg^?1 bupivacaine 0.25% with 5 μg · kg^?1 adrenaline. The dose for caudal anaesthesia was 1 ml · kg^?1 up to 20 ml bupivacaine 0.2% with 5 μg · kg^?1 adrenaline. Postoperative pain was assessed with mCHEOPS in the anaesthesia recovery room, with postoperative usage of opioid and acetaminophen in the hospital, and with parental assessment of pain with a VAS. Vomiting, time to first ambulation and first urination were recorded. The postoperative pain scores and opioid usage were similar; however, the LA-group required more acetaminophen in the Day Care Surgical Unit. The incidence of vomiting and the times to first ambulation and first urination were similar. The LA-patients had a shorter recovery room stay (40 ± 9 vs 45 ± 15 min, P < 0.02). The postoperative stay was prolonged in the CA group (176 ± 32 vs 165 ± 26 min, P = 0.02). We conclude that LA and CA have similar effects on postoperative care with only slight differences.     

Optimizing sedation following major vascular surgery: a double-blind study of midazolam administered by continuous infusion

A randomized, double-blind study was undertaken to determine the dose requirements, recovery characteristics, and pharmacokinetic variables of midazolam given by continuous infusion for sedation in patients following abdominal aortic surgery. Thirty subjects, 50–75 yr, scheduled to undergo aortic reconstructive surgery, entered the study. Following a nitrous oxide-isoflurane-opioid anaesthetic technique, patients were randomly allocated to receive one of three loading doses (0.03, 0.06 or 0.1 mg · kg^?1) and initial infusion rates (0.5, 1.0 or 1.5 μg · kg^?1 · min^?1) of midazolam, corresponding to groups low (L), moderate (M) and high (H). The infusion of midazolam was adjusted to maintain sedation levels of “3, 4 or 5,“ which permitted eye opening in response to either verbal command or a light shoulder tap, using a seven-point scale ranging from “0” (awake, agitated) to “6” (asleep, non-responsive). Additionally, morphine was given in increments of 2.0 mg iv prn for analgesia. On the morning after surgery, midazolam was discontinued, and the tracheas were extubated when patients were awake. Blood samples were taken during, and at increasing intervals for 48 hr following discontinuation of the infusion, and analyzed by gas chromatography. The desired level of sedation was maintained during more than 94% of the infusion period in all three groups, with a maximum of three dose adjustments per patient, for treatment which lasted 16.3 ± 0.6 hr. There was, however, an increase in both the infusion rates and mean plasma concentrations from Group L to Group H (P < 0.05), which corresponded to an inverse relationship of morphine requirements during the period of sedation (P < 0.05, Group H vs Group L). Optimal midazolam infusion rates and resulting plasma concentrations at the times the infusions were discontinued (in parentheses) were as follows — Group L: 0.60 ± 0.18 μg · kg^?1 min^?1 (76 ± 32 ng · mL^?1), Group M: 0.90 ± 0.52 μg · kg^?1 · min^?1 (133 ± 71 ng · mL^?1), and Group H: 1.34 ± 0.69 μg · kg^?1 · min^?1 (206 ± 106 ng · mL^?1). Times to awakening were longer in Group H: 3.1 ± 3.4 hr, than in Group L: 1.1 ± 0.8 h, P < 0.05. Pharmacokinetic variables were found to be dose- independent over the range of infusion rates. Mean values were t_1/2β = 4.4 ± 1.5 hr, CL = 5.94 ± 1.69 mL · min^?1 · kg^?1, Vd = 3.13 ± 1.07 L · kg^?1. It is concluded that midazolam, infused between 0.6–0.9 μg · kg^?1 · min^?1, provides a stable level of sedation, when administered in conjunction with intermittent iv morphine following AAS. This sedation technique, which costs $1.65 ± 0.73 hr^?1 ($Can), is associated with rapid recovery and minimal side effects.     

Atropine-induced heart rate changes: a comparison between midazolam-fentanyl-propofol-N2O and midazolam-fentanyl-thiopentone-enflurane-N2O anaesthesia

Atropine-induced heart rate (HR) changes were studied in 19 patients (ASA physical status I) during anaesthesia maintained predominantly with propofol-N₂O or thiopentone-enflurane-N₂O. Ten patients (Group A) received midazolam (0.07 mg · kg^?1), fentanyl (1 μg · kg^?1), propofol (2 mg · kg^?1) and succinylcholine (1 mg · kg^?1). Following tracheal intubation, anaesthesia was maintained with propofol (6 mg · kg^?1 · hr^?1), N₂O (67 per cent) and O₂ (33 per cent). In nine patients (Group B) thiopentone (4 mg · kg^?1) was substituted for propofol and anaesthesia maintained with N₂O (67 per cent) O₂ (33 per cent), and enflurane (0.5 per cent inspired concentration). The study was non-randomised because Group B patients were only included if HR before administration of atropine < 90 beats · min^?1. IPPV was performed in all patients using a Manley ventilator (minute vol. 85 ml · kg^?1; tidal vol. 7 ml · kg^?1). Ten minutes after tracheal intubation, incremental doses of atropine (equivalent cumulative doses: 1.8, 3.6, 7.2, 14.4, 28.8 μg · kg^?1) were administered at two-minute intervals and HR responses calculated during the last 45 sec of each intervening period. No differences were observed between the groups following 1.8 and 3.6 μg · kg^?1 atropine, but propofol-N₂O anaesthesia was associated with reduced responses (P < 0.01) following 7.2, 14.4 and 28.8 μg · kg^?1 atropine. These results suggest that there is a predominance of parasympathetic influences during propofol-N₂O anaesthesia compared with thiopentone-enflurane-N₂O anaesthesia.     

Plasma concentrations after high-dose (45 mg · kg−1) rectal acetaminophen in children

Although the recommended dose of rectal acetaminophen (25–30 mg · kg^?1) is twice that for oral administration (10–15 mg · kg^?1), the literature justifies the use of a higher dose when acetaminophen is administered via the rectal route. We measured’ venous plasma acetaminophen concentrations resulting from 45 mg · kg^?1 of rectal acetaminophen in ten ASA 1, 15 kg paediatric patients undergoing minor surgery with a standardized anaesthetic. After induction of anaesthesia, a single 650 mg suppository (Abenol®, SmithKline Beecham Pharma Inc.) was administered rectally. Plasma was sampled at t = 0, 15, 30, 45, 60, 90, 120, 180, 240 min in the first five patients and at t = 0, 30, 60, 90, 120, 180, 240, 300, 420 min in the subsequent five. Acetaminophen plasma concentrations were determined’ using a TDxFLx® fluorescence polarization immunoassay (Abbott Laboratories, Toronto, Ontario). The maximum plasma concentration was 88 ± 39 μmol · L^?1 (13 ± 6 μg · ml^?1) and the time of peak plasma concentration was 198 ± 70 min (mean ± SD). At 420 min, the mean plasma concentration was 46 ± 18 μmol · L^?1 (7.0 ± 0.9 μg · ml^?1). No plasma concentrations associated with toxicity (> 800 μmol · L^?1) were identified. A 45 mg · kg^?1 rectal dose of acetaminophen resulted in peak plasma concentrations comparable with those resulting from 10–15 mg · kg^?1 of oral acetaminophen at three hours after suppository insertion. It is concluded that the delayed and erratic absorption of acetaminophen after rectal administration leads to unpredictable plasma concentrations. Rectal acetaminophen will not be consistently effective for providing rapid onset of analgesia in children.     

Oral clonidine premedication reduces vomiting in children after strabismus surgery

This is a prospective randomized double-blind trial conducted to determine whether preoperative orally administered clonidine causes or potentiates postoperative vomiting in 140 children (3–12 yr) undergoing strabismus surgery. They were all inpatients and classified randomly into four groups (n = 35 each); placebo (control), diazepam 0.4 mg · kg^?1, clonidine 2 μg · kg^?1, and clonidine 4 μg · kg^?1. These agents were administered 93–112 min (mean: 100 min) before the anticipated time of induction of anaesthesia. All children received inhalational anaesthesia with halothane and nitrous oxide in oxygen.’ Muscle relaxation in all patients was obtained with vecuronium and residual neuromuscular blockade was antagonized with neostigmine and atropine before tracheal extubation. Diclofenac suppository was prescribed to prevent postoperative pain. No opioids or postoperative antiemetics were administered. All children remained in hospital for two days postoperatively. The incidence and frequency of vomiting were compared in the groups with Kruskall-Wallis Rank test. Clonidine 4 μg · kg^?1 caused a lower incidence and frequency of vomiting than did placebo and diazepam (incidence and frequency: 11% and 1,37% and 3, and 34% and 2 in clonidine 4 μg · kg^?1, placebo, and diazepam, respectively; P < 0.05 for clonidine 4 μg · kg^?1 vs placebo and diazepam). However, lowdose clonidine was ineffective. These data suggest that preanaesthetic medication with clonidine 4 μg · kg^?1 may be useful for preventing emesis following strabismus surgery. This property of clonidine indicates that it may be superior to other sedative premedicants such as diazepam and midazolam.     

Clindamycin-induced neuromuscular blockade

The purpose of this article is to report the case of a patient who developed prolonged neuromuscular block after a large dose of clindamycin (2400 mg). A 58-yr-old, 65 kg woman with severe rheumatoid arthritis was admitted for wrist arthrodesis. After d-tubocurarine (3 mg) and fentanyl (1.5 μg · kg^?1), anaesthesia was indúced with thiopentone (4 mg · kg^?1) followed by succinycholine (1.5 mg · kg^?1) and was maintained with N₂O in O₂ and isoflurane (0.75-1.0% end tidal) and ventilation was controlled. No further neuromuscular relaxants were given although full return of neuromuscular activity in response to train-of-four and 100 Hz tetanic stimulation was observed after succinylcholine. An overdose of clindamycin (2400 mg, instead of the intended 600 mg) was given iv soon after the start of surgery. At the end of surgery, 75 min later, the patient made no attempt at spontaneous ventilation, was unresponsive to painful stimuli and naloxone (0.2 mg iv) was ineffective. Controlled ventilation was continued in the Recovery Room where neuromuscular testing showed a train-of-four ratio of 0.27 which improved to only 0.47 five minutes after calcium chloride (1.5 mg · kg^?1 iv), and to 0.62 after edrophonium (20 mg) and neostigmine (2 mg). Nine hours later the patient began to cough, the TOF had returned to 1.0 and two hours later the trachea was extubated and spontaneous ventilation was resumed. Large doses of clindamycin can induce profound, long-lasting neuromuscular blockade in the absence of non-depolarizing relaxants and after full recovery from succinylcholine has been demonstrated.     

Oral ondansetron decreases vomiting after tonsillectomy in children

Vomiting is a common, unpleasant aftermath of tonsillectomy in children. Intraoperative intravenous ondansetron (OND) reduces vomiting after this operation. Our doubleblind, placebocontrolled, randomized investigation studied the effect of the oral form of OND on vomiting after outpatient tonsillectomy in children. We studied 233 healthy children age 2–14 yr undergoing elective tonsillectomy. Subjects were given placebo (PLAC) or OND 0.1 mg · kg^?1 rounded off to the nearest 2 mg one hr before surgery. Anaesthesia was induced with either propofol or halothane/N₂O. Vecuronium 0.1 mg · kg^?1 was administered at the discretion of the anaesthetist. Anaesthesia was maintained with halothane/N₂O, 50 μg · kg^?1 midazolam iv and 1–1.5 mg · kg^?1 codeine im. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine and atropine. All episodes of inhospital emesis were recorded by nursing staff. Rescue antiemetics in the hospital were 1 mg · kg^?1 dimenhydrinate ivfor vomiting × 2 and 50 μg · kg^?1 droperidol iv for vomiting × 4. Parents kept a diary of emesis after discharge. Postoperative pain was treated with morphine, codeine and/or acetaminophen. The two groups were similar with respect to demographic data, induction technique and anaesthesia time. Oral OND (n = 109) reduced postoperative emesis from 54% to 39%, P < 0.05. This effect was most dramatic inhospital, where 10% of the OND-patients and 30% of the PLAC-group vomited, P < 0.05. The OND-subjects required fewer rescue antiemetics, 7% vs 17%, P < 0.05. In conclusion, oral ondansetron decreased the incidence of vomiting after outpatient tonsillectomy in children.     

Clonidine does not affect lidocaine seizure threshold in rats

We investigated the effect of clonidine on intravenous (iv) lidocaine-induced haemodynamic changes and convulsions in awake rats. Wistar rats (200–250 g) were divided into three groups of eight and were pretreated with iv clonidine or normal saline 15 min before lidocaine infusion. Group 1 received normal saline; Group 2, 1 μg · kg^?1 clonidine; and Group 3, 10 μg · kg^?1 clonidine. After surgical preparation and recovery from anaesthesia, all groups received a continuous iv infusion of lidocaine (15 mg · ml^?1) at a rate of 4 mg · kg^?1 · min^?1 until generalized convulsions occurred. Oxygenation was well maintained in all groups. Pretreatment with clonidine changed neither cumulative convulsant doses (Group 1: 41.8 ± 2.2, Group 2: 43.8 ± 2.6, Group 3: 42.3 ± 2.0 mg · kg^?1, respectively) nor plasma concentrations of lidocaine at the onset of convulsions (Group 1: 10.5 ± 0.3, Group 2: 10.8 ± 0.3, Group 3: 10.6 ± 0.3 μg · ml^?1, respectively). The mean arterial blood pressures in Groups 2 and 3 were decreased after clonidine pretreatment (Group 2: 93 ± 1, P < 0.01, Group 3: 90 ± 1%, P < 0.01, respectively) and they gradually increased during lidocaine infusion. The heart rates decreased after clonidine pretreatment (Group 2: 94 ± 2, P < 0.05, Group 3: 86 ± 2%, P < 0.01, respectively) and the combination of clonidine and lidocaine potentiated the bradycardic effect of lidocaine at a subconvulsant dose. Our results indicate that clonidine has neither anticonvulsant nor proconvulsant effects on lidocaineinduced convulsions. However, the interactions of clonidine and lidocaine on blood pressure and heart rate should be investigated further.     

Oral clonidine does not alter vecuronium neuromuscular blockade in anaesthetized patients

Since clonidine, an α₂-agonist, inhibits the release of norepinephrine or acetylcholine which can decrease nondepolarizing muscle relaxant-induced neuromuscular blockade, the authors examined whether clonidine given as an oral preanaesthetic medication would alter the onset, duration or recovery of a vecuronium neuromuscular blockade in lightly anaesthetized patients. Thirty-eight patients (aged 20–73 yr) randomly received oral clonidine either approximately 5 μg · kg^?1 (n = 21) or none (n = 17), 90 min before arrival in the operating room. We measured acceleration of thumb contraction with ulnar nerve stimulation at the wrist to assess neuromuscular blockade. The onset time (the time from injection to decrease to 5% of baseline twitch height), duration (the time interval between injection and return of the first twitch to 25% of the baseline value), and recovery index (the time interval of the first twitch from 25% to 75% of the baseline value) of neuromuscular blockade from a single bolus of vecuronium 0.1 mg · kg^?1 iv were determined and compared between the clonidine-treated and control patients during lower abdominal or extremity surgery under epidural plus general anaesthesia with fentanyl and nitrous oxide in oxygen. No differences were noted between the control and clonidine groups in onset time (100 ± 6 sec (mean ± SE) vs 101 ± 6 sec), duration (44.5 ±2.7 min vs 42.9 ±2.7 min), or recovery index (21.6 ± 2.8 min vs 19.1 ± 1.9 min) of neuromuscular blockade from vecuronium, respectively. These results show that oral preanaesthetic medication of clonidine 5 μg · kg^?1 does not alter neuromuscular blockade induced with vecuronium 0.1 mg · kg^?1 in patients during combined epidural and fentanyl/nitrous oxide general anaesthesia.     

Displacement of lidocaine from the lung after bolus injection of bupivacaine

The purpose of this study was to determine whether lidocaine was displaced from the lung after bolus injection of bupivacaine. Fourteen anaesthetized rabbits were randomly assigned to either a bupivacaine or a control group. Lidocaine was infused at a rate of 10 mg · kg^?1 hr^?1. After one hour of infusion, a bolus of bupivacaine (1 mg · kg^?1) in normal saline (0.2 ml · kg^?1) was injected into the central venous circulation in the bupivacaine group. The control group was injected with normal saline. After bolus injection, arterial blood samples were collected serially from an internal carotid artery at 1.2-sec intervals for 24 sec. The baseline concentration of lidocaine was 3.0 ±0.1 μg · ml^?1 in the bupivacaine group and 3.2 ±0.1 μg · ml^-1 in the control group (NS). Arterial concentrations of lidocaine increased to a maximum of 4.7 ±0.2 μg · ml^?1 in the bupivacaine group (P = 0.0001). No increases were seen in the control group. These findings indicate that lidocaine was displaced from the lung into the blood after bolus injection of bupivacaine. The amount of lidocaine displaced during the first passage of bupivacaine through the lung was calculated to be 92.3 ±9.7 μg. It is concluded that lidocaine is displaced from the lung after bolus injection of bupivacaine.     

Left ventricular regional wall motion and haemodynamic changes following bolus administration of pipecuronium or pancuronium to adult patients undergoing coronary artery bypass grafting

The objective of this study was to compare the haemodynamic and myocardial effects of pipecuronium and pancuronium in patients undergoing coronary artery bypass grafting (CABG) during benzodiazepine/sufentanil anaesthesia. Twenty-seven ASA III–IV patients received lorazepam (1–3 mg) po and midazolam (<0.1 mg · kg^?1) iv before induction of anaesthesia with sufentanil (3–8 μg · kg^?1). Vecuronium (0.1 mg · kg^?1) was administered to facilitate tracheal intubation. According to random allocation, each patient received either pipecuronium (150 μg · kg^?1) or pancuronium (120 μg · kg^?1) after stemotomy but before heparinization. Mean arterial pressure, central venous pressure (CVP), pulmonary artery pressure (PAP), ST segment position and ECG (leads HI, V₅, AVF) were monitored continuously throughout the procedure. Thermodilution determinations of CO in triplicate were made immediately before, and at two and five minutes after muscle relaxant administration. Multiplane transoesophageal echocardiography (TEE, midpapillary short axis views of the left ventricle) images were continuously recorded from ten minutes before until ten minutes after muscle relaxant administration and graded by two experienced echocardiographic readers. Heart rate, MAP and CO increased after administration of pancuronium (by 13.6 beats · min^?1, 10.8 mmHg and 1.0 L · min^?1 respectively) but not after pipecuronium (P < 0.05). Evidence of myocardial ischaemia was not detected in any patients using ECG ST segment analysis or TEE assessment of left ventricular wall motion. We conclude that pancuronium caused increases in HR, MAP and CO but that neither pancuronium nor pipecuronium caused myocardial ischaemia.     

Propofol anaesthesia reduces early post-operative emesis after paediatric strabismus surgery

Propofol anaesthesia may reduce postoperative emesis. The purpose of this study was to compare the incidence of emesis after propofol anaesthesia with and without nitrous oxide, compared with thiopentone and halothane anaesthesia, in hospital and up to 24 hr postoperatively, in outpatient paediatric patients after strabismus surgery. Seventy-five ASA class I or II, unpremedicated patients, aged 2–12 yr were randomly assigned to one of three groups: Thiopentone, 6.0 mg · kg^{? 1} iv induction followed by halothane and N₂O/O₂ for maintenance (T/H); propofol for induction, followed by propofol and oxygen for maintenance (P/O₂); and propofol for iv induction, followed by propofol infusion and N₂O/O₂ for maintenance (P/N₂O). All received vecuronium, controlled ventilation, and acetaminophen pr. Morphine was given as needed for postoperative analgesia. There were no differences in age, weight, number of eye muscles operated upon, duration of anaesthesia or surgery. The P/N₂O group (255 ± 80 μg· kg^{? 1}· min^{? 1}) received less propofol than the P/O₂ group (344 ± 60 μg · kg^{? 1}· min^{? 1}) (P ≤ 0.0001) and had shorter extubation (P < 0.001) and recovery (P < 0.01) times. Emesis in the hospital, in both the P/N₂O (4.0%) and P/O₂ group (4.0%) was less than in the T/H group (32%) (P < 0.01). Antiemetics were required in four patients in the T/H group (16.0%). Overall emesis after surgery was not different among the groups: T/H (48%), P/O₂ (28%) and P/N₂O (42%). The use of propofol anaesthesia with and without N₂O decreased only early emesis. This supports the concept of a short-acting, specific antiemetic effect of propofol.     

Haemodynamic instability and myocardial ischaemia during carotid endarterectomy: A comparison of propofol and isoflurane

The purpose of this study was to compare two anaesthetic protocols for haemodynamic instability (heart rate (HR) or mean arterial pressure (MAP) <80 or > 120% of ward baseline values) measured at one-minute intervals during carotid endarterectomy (CEA). One group received propofol/alfentanil (Group Prop; n = 14) and the other isoflurane I alfentanil (Group Iso; n = 13). Periods of haemodynamic instability were correlated to episodes of myocardial ischaemia as assessed by Holler monitoring (begun the evening before surgery and ceasing the morning of the first postoperative day). In Group Prop, anaesthesia was induced with alfentanil 30 μg · kg^?1 rv, propofol up to 1.5 mg · kg^?1 and vecuronium 0.15 mg · kg^?1, and maintained with infusions of propofol at 3–12 mg · kg^?1· hr^?1 and alfentanil at 30 μg · kg^?1 · hr^?1. In Group Iso, anaesthesia was induced with alfentanil and vecuronium as above, thiopentone up to 4 mg · kg^?1 and maintained with isoflurane and alfentanil infusion. Phenylephrine was infused to support MAP at 110 ± 10% of ward values during cross-clamp of the internal carotid artery (ICA) in both groups. Emergence hypertension and/or tachycardia was treated with labetalol, diazoxide or propranolol. Myocardial ischaemia was defined as ST-segment depression of >-1 mm (60 msec past the J-point) persisting for >-one minute. For the entire anaesthetic course (induction to post-emergence), there was no difference between groups for either duration or magnitude outside the <80 or >120% range for HR or MAP. However, when the period of emergence from anaesthesia (reversal of neuromuscular blockade to post-extubation) was assessed, more patients were hypertensive (P = 0.004) and required vasodilator therapy in Group Iso (10/ 13 vs 5/14; P = 0.038 Fisher’s Exact Test). The mean dose of labetalol was greater in Group Iso (P = 0.035). No patient demonstrated myocardial ischaemia during ICA cross-clamp. On emergence, 6/13 patients in Group Iso demonstrated myocardial ischaemia compared with 1/14 in Group Prop (P = 0.029). Therefore, supporting the blood pressure with phenylephrine, during the period of ICA cross-clamping, appears to be safe as we did not observe any myocardial ischaemia at this time. During emergence from anaesthesia, haemodynamic instability was associated with myocardial ischaemia. Under these specific experimental conditions, with emergence, hypertension and myocardial ischaemia were more prevalent with more frequent pharmacological interventions in patients receiving isoflurane.     

Attenuation of the catecholamine response to tracheal intubation with oral clonidine in children

We conducted a prospective, randomized, double-blind, controlled clinical trial to examine (1) whether plasma catecholamine (CA) concentrations increased in response to tracheal intubation in children, and (2) the effects of clonidine on the CA responses. Sixty children (ASA physical status I) aged 7– 13 yr were allocated to one of three groups (n = 20 for each group): diazepam 0.4 mg · kg^{? 1} (active control), clonidine 2 μg · kg^{? 1}, or clonidine 4 μg · kg^{? 1} po. These agents were administered 105 min before induction of anaesthesia followed by oral atropine 0.03 mg · kg^{? 1} given 60 min before anaesthesia which was induced with thiamylal 5 mg · kg^{? 1} and tracheal intubation was facilitated with vecuronium 0.2 mg · kg^{? 1}. Laryngoscopy, lasting 30 sec, was attempted two minutes after administration of the induction agents. Serial values for blood pressure, heart rate, and venous plasma CA concentrations were compared among the three groups and with the respective preinduction measurements. Children receiving diazepam or clonidine 2 μg · kg^{? 1} showed remarkable increases in systolic and diastolic blood pressures, heart rate, and plasma CA concentrations in response to tracheal intubation (P < 0.05). The increases were similar for the two regimens. These haemodynamic and CA changes were smaller in children receiving clonidine 4 μg · kg^{? 1} (P < 0.05). The haemodynamic responses were positively correlated with the CA responses. These findings indicate that tracheal intubation following rapid sequence induction of anaesthesia in children provokes a reflex increase in sympathetic activity characterized by increased plasma CA concentrations, and that attenuation of the cardiovascular changes with a high oral dose of clonidine may be due to suppression of the increase in sympathetic activity evoked by the intubation.     

RETRACTED ARTICLE: Optimal anti-emetic dose of granisetron for preventing post-operative nausea and vomiting

In order to determine the optimal effective dose of granisetron for preventing postoperative nausea and vomiting, the drug was administered in doses of either 20, 40 or 60 μg sd kg^?1. The efficacy of granisetron was evaluated in a randomized, double-blind comparison with placebo in 100 patients undergoing general anaesthesia for major gynaecological surgery. The patients received a single dose of either granisetron or placebo (saline) iv immediately after recovery from anaesthesia. The effects were assessed during the 24 hr after recovery from anaesthesia by means of a nausea and vomiting score; 0 = no emetic symptoms, 1 = nausea, 2 = vomiting. The treatment groups were similar for patient characteristics, surgical procedures and anaesthetics administered. The mean scores were 0.7, 0.6, 0.2 and 0.2 after administration of placebo, granisetron 20, 40 and 60 μg · kg^?1, respectively. Granisetron 40 μg · kg^?1 was as effective as 60 μg · kg^?1 and both resulted in reduction of the scores compared with placebo and granisetron 20 μg · kg^?1 (P < 0.05). In conclusion, granisetron 40 μg · kg^?1 is considered to be the appropriate dosage for preventing postoperative emesis after anaesthesia.     

Modification of intravenous lidocaine-induced convulsions by epinephrine in rats

We studied intravenous lidocaine-induced convulsions in rats to determine whether added epinephrine influences the provocation of lidocaine toxicity. Wistar rats (200–250 g) were divided into three groups of ten, depending on the concentration of epinephrine added to lidocaine. Group 1: plain 1.5% lidocaine; Group 2: 1.5% lidocaine with 1∶200,000 epinephrine; Group 3: 1.5% lidocaine with 1∶100,000 epinephrine. After surgical preparation and recovery from anaesthesia, all rats received a continuous iv infusion of lidocaine (15 mg·ml^?1) at a rate of 4.0 mg·kg^?1·min^?1 until generalized convulsions occurred. The epinephrine-treated animals developed acute hypertension after one minute of lidocaine infusion (105±2 to 141±2 mmHg in Group 2 and 103±2 to 151±2 mmHg in Group 3). The PaO₂ values in the epinephrine groups at the onset of convulsions were decreased significantly (88.3±1.0 to 84.0 ±1.5 mmHg in Group 2 P < 0.05 and 86.9±1.2 to 78.1±2.4 mmHg in Group 3 P<0.01). However, these values were still within physiological ranges. Serum potassium concentrations in all groups were decreased P<0.05, (4.24±0.09 to 3.52±0.12 mEq·L^?1 in Group 1, 4.02±0.09 to 3.63±0.17 mEq·L^?1 in Group 2, and 4.15±0.10 to 3.69 ±0.17 mEq·L^?1 in Group 3). Blood sugar concentrations in all groups were increased at the onset of convulsions, and the levels in the epinephrine groups were higher than in Group 1 P<0.01 (119±4 to 149±7 mg·dl^?1 in Group 1: 120±4 to 195±10 mg·dl^?1 in Group 2, and 127±3 to 190±6 mg·dl^?1 in Group 3). There were differences in the cumulative convulsant doses of lidocaine among the groups, as follows: Group 1=41.9±1.3 > Group 2=30.0±0.7 > Group 3=24.2±0.9 mg·kg^?1; P<0.01. At the onset of convulsions, not only the plasma lidocaine concentrations (Group 1=10.7±0.3 > Group 2=8.3±0.2 (P<0.01) > Group 3=7.5±0.2 μg·ml^?1 (P<0.01 vs Group 1, P < 0.05 vs Group 2), but also the brain lidocaine concentrations which were extracted from the whole brain homogenates: Group 1=48.7±1.9 > Group 2=38.2±1.1 (P<0.01) > Group 3=33.0±1.3 μg·g^?1 (P <0.01 vs Group 1, P<0.05 vs Group 2) showed differences. The brain/plasma lidocaine concentration ratios were, however, similar in the three groups (Group 1=4.5±0.1; Group 2=4.6±0.1; Group 3=4.4±0.2). Our data show that added epinephrine decreases the threshold of lidocaine-induced convulsions dose-dependently; however, the added ephinephrine does not cause a greater proportion of the infused lidocaine to enter the CNS.     

Propranolol pretreatment reduces cardiorespiratory toxicity due to plain,but not epinephrine-containing,intravenous bupivacaine in rats

The purpose of this study was to evaluate the effects of pretreatment with propranolol on the cardio-respiratory toxicity of bupivacaine, either plain or with epinephrine 1:200,000 (5 μg · ml^{? 1}) added. Adult male Sprague Dawley rats, anaesthetized with intraperitoneal pentobarbital, were divided into four groups. Groups I and III were pretreated with iv propranolol 150 μg · kg^{? 1}, and Groups II and IV recei ved iv NS as a placebo. Three minutes later, rats in Groups I and II received plain 0.5% bupivacaine, 4 mg · kg^{? 1}, and Groups III and IV received 4 mg· kg^{? 1} of 0.5% bupivacaine with epinephrine, 5 μg · ml^{? 1} iv. Five of eight rats pretreated with propranolol survived (Group I), compared with uniform fatality with NS pretreatment (Group II) (P < 0.05). Addition of epinephrine to the bupivacaine eliminated the protective effect of propranolol. All rats pretreated with propranolol (Group III) or NS (Group IV) died when given bupivacaine with epinephrine. In conclusion, acute propranolol pretreatment reduced the fatal cardiotoxicity due to iv bupivacaine in male Sprague Dawley rats, but the addition of epinephrine 5 μg · ml^{? 1} to bupivacaine eliminated the protective effect of propranolol.     

Safety and efficacy of alfentanil and halothane in paediatric surgical patients

Alfentanil, a congener of the opioid fentanyl, possesses properties that make it an attractive choice for use during short operative procedures. Since the phannacodynamic aspects of alfentanil have not been well documented in children, this study was undertaken to evaluate the safety, efficacy, and dose requirements of alfentanil when used with nitrous oxide or halothane in paediatric patients. Eighty unpremedicated patients, ASA physical status I or II and aged 2–12 yr were studied. Patients were randomly assigned to one of four groups. After induction of anaesthesia with nitrous oxide, oxygen, and halothane, the groups were treated as follows. In Group I (n = 19), after halothane was discontinued, alfentanil 50 μg · kg^?1 was infused over 30 sec. In Group 2 (n = 20), the end-tidal halothane was maintained at 0.5% and alfentanil 25 μg · kg^?1 was infused. In Group 3 (n = 20), the end-tidal halothane concentration was maintained at 1% and alfentanil 12.5 μg · kg^?1 was infused. In Group4(n = 21), the end-tidal halothane concentration was maintained at 1.5% and no alfentanil was administered. Patients in Groups 1, 2, and 3 received bolus doses of alfentanil 12.5 μg · kg^?1 as needed to maintain haemodynamic stability. After alfentanil administration, there were transient decreases in systolic blood pressure in Groups 1 and 2, and in heart rate in Group 2. With surgical stimulation, haemodynamic stability was well maintained except in patients in Group 1, who had an increase in systolic blood pressure. Children Group 1 were alert sooner and their tracheas were extubated earlier than those in Groups 2, 3, and 4. The four groups were similar in postoperative narcotic analgesic administration and incidence of vomiting. In summary, alfentanil (12.5–50.0 μg · kg^?1) was a safe anaesthetic, whether combined with nitrous oxide alone or with nitrous oxide and halothane.