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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Nicardipine and verapamil attenuate the pressor response to laryngoscopy and intubation

In a prospective, double-blind study, we compared the efficacy of iv nicardipine hydrochloride and verapamil hydrochloride in attenuating the cardiovascular responses to laryngoscopy and tracheal intubation, in 45 patients undergoing elective surgery with general anaesthesia. Patients were allocated randomly to one of three groups of 15 patients. Patients in Group I received saline while those in Groups II and III received nicardipine hydrochloride, 0.03 mg · kg^{? 1} or verapamil hydrochloride, 0.1 mg · kg^{? 1} iv three minutes before laryngoscopy and intubation. Patients in Group I showed the greatest increase in SBP 25.4 ± 2.2 mmHg and HR 35.7 ± 3.8 beats · min^{? 1} at one minute after intubation (P < 0.001), and these changes persisted throughout the study period albeit with decreasing magnitude. After drug administration, patients in Groups II and III demonstrated increases in HR of 26 ± 2.4 and 15.1 ± 2.2 beats · min^{? 1} and decreases in SBP of 24.8 ± 2.0 and 18.8 ± 2.4 mmHg respectively (P < 0.001). It is concluded that nicardipine and verapamil are effective in attenuating pressor responses to laryngoscopy and intubation but did not control the tachycardia.     

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.     

Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury

Myocardial ischaemia is one of the major causes of low output syndrome during open heart surgery. Injury associated with ischaemia and reperfusion has been considered to result, in part, from the action of neutrophils, the interaction of neutrophils with vascular endothelial cells, and the effects of cytokines which are mediators that induce and modify reactions between these substances. We investigated cell injury in relation to the concentrations of interleukins 6 and 8 (IL-6 and IL-8), which have recently received attention as neutrophil activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour necrosis factor-α (TNF-α), CK, and CK-MB concentrations were determined serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Neutrophil counts (mean ±SD 2717 ±2421 μl^?1 preoperatively) peaked 60 min after declamping the aorta at 7432 ±4357 μl^?1 (P < 0.01) and remained elevated 7136 ±5194 μl^?1 at 180 min (P < 0.01). Plasma GEL level (168 ±71 μg sd L^?1 preoperatively) peaked at 1134 ±453 μg · L^?1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 ±467 μg · L^?1, after 180 min (P < 0.01). Serum IL-6 level (118 ±59 pg · ml^?1 preoperatively) peaked at 436 ±143 pg · ml^?1 60 min after declamping of the aorta (P < 0.01) and remained elevated, 332 ±109 pg · ml^?1, after 180 min. Serum IL-8 level (37 ±44 pg · ml^?1 preoperatively) peaked at 169 ±86 pg · ml^?1 at 60 min after declamping of the aorta (P < 0.001) and remained elevated at 113 ±78 pg · ml^?1 180 min after declamping of the aorta. Serum TNF-α was decreased at 60 min after aortic occlusion but otherwise did not change. Plasma GEL concentrations correlated with serum IL-8 levels (R = 0.7, P = 0.001) and the IL-6 and IL-8 concentrations correlated with the duration of aortic clamping (R = 0.64, P = 0.01, R = 0.7, P = 0.01). We conclude that the increases of IL-6 and IL-8 occur as a result of ischaemia, and suggest that these cytokines participate in reperfusion injury by activating neutrophils.     

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.     

A comparative study of patient-controlled epidural fentanyl and single dose epidural morphine for post-caesarean analgesia

In a prospective, randomized, double-blinded study, 23 patients who had undergone Caesarean delivery under epidural anaesthesia were assessed to evaluate the effectiveness of patientcontrolled epidural analgesia (PCEA) with fentanyl compared with a single dose of epidural morphine for postoperative analgesia. Group A (n = 11) received epidural fentanyl 100 μg intraoperatively, then self-administered a maximum of two epidural fentanyl boluses 50 μg (10 μg · ml^?1) with a lockout period of five minutes for a maximum of two doses per hour. Group B (n = 11) received a single bolus of epidural morphine 3 mg (0.5 mg · ml^?1) intraoperatively and received the same instructions as Group A but had their PCA devices filled with 0.9% NaCl. Patients were assessed up to 24 hr for pain, satisfaction with pain relief, nausea and pruritus using visual analogue scales (VAS). The treatments for inadequate analgesia, nausea and pruritus as well as time to first independent ambulation were recorded. The ventilatory response to carbon dioxide challenge was measured at four and eight hours. Pain relief, satisfaction with pain relief, and the use of supplemental analgesics were similar in both groups. The mean 24 hr dose of epidural fentanyl used by group A patients was 680 μg. Pruritus was less common in Group A patients at the 8 and 24 hr observation periods (P < 0.0125). Both groups experienced the same degree of nausea and clinically unimportant respiratory depression. We conclude that PCEA with fentanyl provides analgesia equal to a single dose of epidural morphine and may be suitable for patients who have experienced considerable pruritus after epidural morphine adminstration.     

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.     

Thiopentone pretreatment for propofol injection pain in ambulatory patients

This study investigated propofol injection pain in patients undergoing ambulatory anaesthesia. In a randomized, double-blind trial, 90 women were allocated to receive one of three treatments prior to induction of anaesthesia with propofol. Patients in Group C received 2 ml normal saline, Group L, 2 ml, lidocaine 2% (40 mg) and Group T, 2 ml thiopentone 2.5% (50 mg). Venous discomfort was assessed with a visual analogue scale (VAS) 5–15 sec after commencing propofol administration using an infusion pump (rate 1000 μg · kg^?1 · min^?1). Loss of consciousness occurred in 60–90 sec. Visual analogue scores (mean ± SD) during induction were lower in Groups L (3.3 ± 2.5) and T (4.1 ± 2.7) than in Group C (5.6 ± 2.3); P = 0.0031. The incidence of venous discomfort was lower in Group L (76.6%; P < 0.05) than in Group C (100%) but not different from Group T (90%). The VAS scores for recall of pain in the recovery room were correlated with the VAS scores during induction (r = 0.7045; P < 0.0001). Recovery room discharge times were similar: C (75.9 ± 19.4 min); L 73.6 ± 21.6 min); T (77.1 ± 18.9 min). Assessing their overall satisfaction, 89.7% would choose propofol anaesthesia again. We conclude that lidocaine reduces the incidence and severity of propofol injection pain in ambulatory patients whereas thiopentone only reduces its severity.     

Pharmacodynamic behaviour of rocuronium in the elderly

This study compared the potency and time course of action of rocuronium (ORG 9426) in elderly and young patients during nitrous oxide-opioid anaesthesia. One hundred ASA physical status I– II patients (60, âgéd 65–80 yr, and 40, âgéd 20–45 yr) were studied by measuring the force of contraction of the adductor pollicis in response to train-of-four stimulation of the ulnar nerve. After induction of anaesthesia with thiopentone and maintenance with N₂O/O₂ and fentanyl, rocuronium 120,160, 200, or 240 μg · kg ^?1 was administered to determine dose-response curves. When maximum block had been obtained,further rocuronium to a total of 300 μg · kg ^?1 was given. Additional doses of 100 μg · kg^?1 were administered when the first twitch height (T₁) had recovered to 25% control. At the end of surgery neuromuscular blockade was allowed, whenever possible, to recover spontaneously until T₁ was 90% of control before administration of neostigmine. There was no difference in the potency of rocuronium in the elderly and the younger patients. The ED₅₀ was 196 ±8 (SEE for the mean) in elderly,vs 215 ±17 iμg · kg ^{? 1} in young patients (NS). When individual cumulative dose-response curves were constructed, the ED₅₀ was 203 ± 7(SEM) and 201 ± 10 μg · kg ^{? 1} in the elderly and the young respectively (NS). However, the onset of maximum neuromuscular block was slower in the elderly 3.7 ±1.1 (SD) vs 3.1 ± 0.9 min, P < 0.05). The time to 25% T ₁ recovery was longer in the elderly (11.8 ± 8.1 vs 8.0 ± 6.5 min,P <0.05) as was the recovery index, time from 25 to 75% T₁ recovery (15.5 ± 6.2 vs 11.2 ± 4.9 min, P< 0.05). The duration of neuromuscular block after each maintenance dose was longer in the elderly (P <0.01) and increased gradually with time. It is concluded that rocuronium is an intermediate-acting neuromuscular blocking drug with a similar potency in elderly and young patients, but the onset and recovery of neuromuscular blockade are slower in the elderly.     

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.     

Bupivacaine kinetics during hyperthermia in rats

The aim of this study was to document possible alterations of bupivacaine pharmacokinetic behaviour in rats during hyperthermia. Two groups of Wistar AF IOPS male rats (Group A = normothermic controls, Group B = hyperthermia-induced animals) received a single 20 mg · kg^?1 ip dose of bupivacaine. Two other groups (Group C = normothermic controls without bupivacaine, Group D = hyperthermia-induced animals without bupivacaine) received, under the same experimental conditions, an equivalent volume of saline. Hyperthermia-induced animals (Groups B and D) were placed in a water-bath at 40° C. Bupivacaine or saline were administered (Group B and D)four hours after the beginning of the experiment and blood samples were obtained by retro-orbital sinus puncture 0.25, 0.5, 1, 2, 4 and 8 hr after administration. Bupivacaine and its main metabolite, 2,6 desbutylbupivacaine (PPX) were assayed according to a gas liquid chromatographic method. The Cmax, Tmax, t_1/2, Cl, Vd and AUC were determined according to a two compartment open model. Our data have demonstrated a decrease in clearance of bupivacaine (5.85 ± 0.23 ml · hr^?1 and 4.59 ± 0.35 ml · hr^?1 for groups A and B, respectively, P < 0.05, and, Tmax of PPX during hyperthermia (0.24 ± 0.03 hr and 0.15 ± 0.0 hr for Groups A and B, respectively, P < 0.05). In conclusion, hyperthermia induces a decrease in bupivacaine clearance in rats which may be of importance in clinical practice.     

Morphine does not affect the awakening concentration of sevoflurane

This study was designed to determine whether morphine 0.1 mg·kg^?1 iv given intraoperatively altered the end-tidal concentration of sevoflurane which is associated with eye opening to verbal command. We studied 24 healthy ASA physical status I patients to determine whether morphine, or placebo administered about 60 min before the end of surgery affected recovery from sevoflurane/oxygen anaesthesia. During anaesthesia no other anaesthetics or drugs were given. After surgery, end-tidal sevoflurane concentration was reduced gradually at the rate of less than 0.01% · min^?1. The end-tidal concentration at the time patients could respond to verbal command was recorded as MACawake. The MACawake was 0.58 ± 0.12% (mean ±SD) for the control group to whom placebo had been administered, and 0.57 ± 0.11% for morphine group to whom morphine had been administered. In both groups, the MACawake decreased with age, and the ratio to age-adjusted sevoflurane MAC was 0.31 ± 0.04 (mean ± SD) for the control group and 0.30 ± 0.04 for the morphine group. The ratio had no correlation with age. It is concluded that the awakening concentration of sevoflurane during recovery from anaesthesia is not affected by analgesic doses of morphine 0.1 mg · kg^?1 iv administered intraoperatively.     

Isoflurane compared with nitrous oxide anaesthesia for intraoperative monitoring of somatosensory-evoked potentials

Intraoperative monitoring of somatosensoryevoked potentials is a routine procedure. To determine the depressant effect of nitrous oxide relative to isoflurane, the authors recorded the scalp, cervical and brachial plexusevoked responses to stimulation of the median nerve under different anaesthetic conditions. Eight subjects, age 35 ± 6 (SD) yr, weight 68 ± 12 kg, were studied. Following recording of awake control responses, anaesthesia was induced with thiopentone 5 mg· kg^{? 1} and fentanyl 3 μg· kg^{? 1} and was followed by succinylcholine 1 mg· kg^{? 1}. During normocapnia and normothermia, and with a maintenance infusion of fentanyl 3 μg · kg^{? 1}· hr^{? 1}, evoked potential recording was repeated under three different anaesthetic conditions; 0.6 MAC nitrous oxide, 0.6 MAC nitrous oxide ± 0.6 MAC isoflurane, and 0.6 MAC isoflurane. Among the anaesthetic conditions, the combination of nitrous oxide-isoflurane had the most depressant effect on the cortical amplitude (67 ± 4% reduction, P < 0.05). Nitrous oxide decreased the cortical amplitude more than an equipotent dose of isoflurane (60 ± 4% vs 48 ± 7%, P < 0.05). The latency was unchanged by nitrous oxide, but increased slightly by isoflurane and isofluranenitrous oxide anaesthesia (1.0 and 0.9 msec respectively, P < 0.05). We conclude that somatosensory-evoked potential monitoring is feasible both during nitrous oxide anaesthesia and isoflurane anaesthesia, but the cortical amplitude is better preserved during 0.6 MAC of isoflurane alone relative to 0.6 MAC of nitrous oxide alone. The depressant effect is maximal during nitrous oxideisoflurane anaesthesia but less than the predicted additive effect.