MAC-AWAKE OF ISOFLURANE, ENFLURANE AND HALOTHANE EVALUATED BY SLOW AND FAST ALVEOLAR WASHOUT

End-tidal anaesthetic concentrations at first eye opening in response to a verbal command during recovery from anaesthesia (MAC-awake), were measured for isoflurane (n = 16), enflurane (n = 16) and halothane (n = 14). MAC-awake was measured during either slow or fast alveolar washout. Slow washout was obtained by decreasing anaesthetic concentrations in predetermined steps of 15min, assuming equilibration between brain and alveolar partial pressures. Fast alveolar washout was obtained by discontinuation of the inhalation anaesthetic, which had been maintained at 1 MAC for at least 15 min. Mean MAC-awake obtained with slow alveolar washout was similar for isoflurane (0.25 (SD 0.03) MAC), and enflurane (0.27 (0.04) MAC) and significantly greater than values obtained by fast alveolar washout (isoflurane: 0.19 (0.03) MAC; enflurane: 0.20 (0.03) MAC). The MAC-awake of isoflurane and enflurane was significantly less than that of halothane, which was 0.59 (0.10) MAC as evaluated by the slow and 0.50 (0.05) MAC as evaluated by the fast alveolar washout method. Recovery time from anaesthesia with fast alveolar washout was 8.8 (4.0) min for halothane, which was not different from isoflurane (15 (2.5) min), but significantly shorter than for enflurane (22 (10) min), reflecting differences in the anaesthetic concentration gradient between MAC and MAC-awake values. These data do not support the hypothesis of a uniform ratio between MAC and MAC-awake value

Propofol 1% versus propofol 2% in children undergoing minor ENT surgery

Background. The induction characteristics of propofol 1% and 2% were compared in children undergoing ENT surgery, in a prospective, randomized, double‐blind study. Methods. One hundred and eight children received propofol 1% (n=55) or 2% (n=53) for induction and maintenance of anaesthesia. For induction, propofol 4mgkg-1 was injected at a constant rate (1200mlh-1), supplemented with alfentanil. Intubating conditions without the use of a neuromuscular blocking agent were scored. Results. Pain on injection occurred in 9% and 21% of patients after propofol 1% and 2%, respectively (P=0.09). Loss of consciousness was more rapid with propofol 2% compared with propofol 1% (47s vs 54s; P=0.02). Spontaneous movements during induction occurred in 22% and 34% (P=0.18), and intubating conditions were satisfactory in 87% and 96% (P=0.19) of children receiving propofol 1% or 2%, respectively. There were no differences between the two groups in respect of haemodynamic changes or adverse events. Conclusions. For the end‐points tested, propofol 1% and propofol 2% are similar for induction of anaesthesia in children undergoing minor ENT surgery. Br J Anaesth 2003: 90: 375-

Interaction of magnesium sulphate with vecuronium-induced neuromuscular blockt

We have investigated the interaction between magnesium sulphate 40 mg kg−1 i.v. and vecuronium. First, we determined the effect of pretreatment with magnesium on the potency of vecuronium using a single bolus dose-response technique. In addition, we compared the time course of vecuronium-induced neuromuscular block (vecuronium 100 μg kg−1) with and without magnesium pretreatment. For both parts, neuromuscular block was assessed by electromyography. In addition, the effect of magnesium pretreatment on vecuronium-induced neuromuscular block was investigated in the context of rapid sequence induction of anaesthesia. We found that the neuromuscular potency of vecuronium was increased by pretreatment with magnesium sul phate. The ED50 and ED90 of vecuronium with MgSO4 were 25% lower than without MgSO4 (ED50 21.3 vs 26.9 μg kg−1 ED90 34.2 vs 45.7 μg kg−1 P < 0.05 for both). Mean onset time was 147.3 (SD 22.2) s in the MgSO4 group vs 297.3 (122) s for controls (P < 0.05). Clinical duration was prolonged (MgSO4-vecuronium 43.3 (9) min vs 25.2 (5.1) min for controls; P < 0.05). This was also true for the recovery index (20.1 (6.6) mm vs 10.6 (3.4) min; P < 0.05) and duration to 75% recovery (63.4 (9.9) min vs 35.8 (6.9) min; < 0.05). In the context of rapid sequence induction, pretreatment with MgSO4 improved the intubating score of vecuronium compared with vecuronium without MgSO4 reach ing the same quality as that with suxamethonium 1 mg kg−1. We conclude that magnesium pretreat ment increased the neuromuscular potency of vecuronium, in addition to modifying the time course of its neuromuscular bloc

PREOPERATIVE SEDATION BEFORE REGIONAL ANAESTHESIA: COMPARISON BETWEEN ZOLPIDEM, MIDAZOLAM AND PLACEBO

The quality of premedication induced by oral midazolam and zolpidem, a new imidazopyridine hypnotic, was assessed in a controlled, double-blind study in 93 patients undergoing elective surgery under spinal or extradural anaesthesia. The patients were allocated randomly to three groups. Each group received the same treatment twice at two different doses. The night before operation, patients received zolpidem 10 mg, midazolam 7.5 mg or placebo and, 1 h before operation, zolpidem 20 mg, midazolam 15 mg or placebo. The sleep inducing effects of the drugs were comparable. Zolpidem and midazolam were significantly more effective sedatives than placebo 45 min after administration, but no difference was noted between the drugs. There was a comparable incidence of anterograde amnesia with zolpidem and midazolam, but the onset was shorter after zolpidem. Side effects were comparable in the three groups. Zolpidem is an effective hypnotic with a rapid onset and short duration of action which may be an alternative to midazolam for premedicatio

DOSE REQUIREMENTS AND PLASMA CONCENTRATIONS OF PIPECURONIUM DURING BILATERAL RENAL EXCLUSION AND ORTHOTOPIC LIVER TRANSPLANTATION IN PIGS

We have studied five pigs undergoing bilateral clamping of the renal pedicles, seven pigs undergoing orthotopic liver transplantation and three control animals without surgery in order to examine the roles of the kidney and liver in the plasma clearance of pipecuronium. An i.v. infusion of pipecuronium was controlled to maintain a constant 90-95 % twitch depression throughout the investigation. The right sciatic nerve was stimulated continuously with supra-maximal stimuli at 0.1 Hz and the force of the corresponding evoked isometric muscle contraction was recorded continuously. Control pigs needed an infusion rate of pipecuronium 8-10.7 μg kg−1 min−1. In the renal group, it was necessary to reduce the infusion rate of pipecuronium by about 25% after clamping both renal vascular pedicles (P < 0.05 compared with controls); in pigs undergoing liver transplantation, it was necessary to reduce the rate by approximately 80% after clamping hepatic vessels (P < 0.05 compared with controls and from the period after clamping of renal vessels). After hepatic recirculation, the infusion rate of pipecuronium was increased progressively to a rate which corresponded to 50% of baseline values (P < 0.05 compared with the anhepatic phase and from controls). Plasma concentrations of pipecuronium were comparable in the three animal groups and did not change significantly during the study. These data suggest that the liver plays a more important role than the kidney in the plasma clearance of pipecuronium in pig

Signal Transduction Pathways in the Pentameric Ligand-Gated Ion Channels

The mechanisms of allosteric action within pentameric ligand-gated ion channels (pLGICs) remain to be determined. Using crystallography, site-directed mutagenesis, and two-electrode voltage clamp measurements, we identified two functionally relevant sites in the extracellular (EC) domain of the bacterial pLGIC from Gloeobacter violaceus (GLIC). One site is at the C-loop region, where the NQN mutation (D91N, E177Q, and D178N) eliminated inter-subunit salt bridges in the open-channel GLIC structure and thereby shifted the channel activation to a higher agonist concentration. The other site is below the C-loop, where binding of the anesthetic ketamine inhibited GLIC currents in a concentration dependent manner. To understand how a perturbation signal in the EC domain, either resulting from the NQN mutation or ketamine binding, is transduced to the channel gate, we have used the Perturbation-based Markovian Transmission (PMT) model to determine dynamic responses of the GLIC channel and signaling pathways upon initial perturbations in the EC domain of GLIC. Despite the existence of many possible routes for the initial perturbation signal to reach the channel gate, the PMT model in combination with Yen's algorithm revealed that perturbation signals with the highest probability flow travel either via the β1-β2 loop or through pre-TM1. The β1-β2 loop occurs in either intra- or inter-subunit pathways, while pre-TM1 occurs exclusively in inter-subunit pathways. Residues involved in both types of pathways are well supported by previous experimental data on nAChR. The direct coupling between pre-TM1 and TM2 of the adjacent subunit adds new insight into the allosteric signaling mechanism in pLGICs. © 2013 Mowrey et al

NOMA: A Preventable “Scourge” of African Children

Noma is a serious orofacial gangrene originating intraorally in the gingival-oral mucosa complex before spreading extraorally to produce a visibly destructive ulcer. Although cases of noma are now rarely reported in the developed countries, it is still prevalent among children in third world countries, notably in sub-Sahara Africa, where poverty, ignorance, malnutrition, and preventable childhood infections are still common. This review summarizes historical, epidemiological, management, and research updates on noma with suggestions for its prevention and ultimate global eradication. The global annual incidence remains high at about 140,000 cases, with a mortality rate exceeding 90% for untreated diseases. Where the patients survive, noma defects result in unsightly facial disfigurement, intense scarring, trismus, oral incompetence, and social alienation. Although the etiology has long been held to be infectious, a definitive causal role between microorganisms cited, and noma has been difficult to establish. The management of noma with active disease requires antibiotics followed by reconstructive surgery. Current research efforts are focused towards a comprehensive understanding of the epidemiology, and further elucidation of the microbiology and pathogenesis of noma

Magnesium sulphate enhances residual neuromuscular block induced by vecuronium

Magnesium sulphate (MgSO4) is currently used for haemodynamic control during anaesthesia and the early postoperative period. We have investigated the effect of this treatment on residual neuromuscular block after administration of vecuronium. Twenty adult patients were allocated randomly to one of two groups to receive MgSO4 60 mg kg-1 either at recovery from vecuronium block to a train-of-four (TOF) ratio of 0.7, or 1 h after recovery to a TOF ratio of 0.7. Neuromuscular transmission was monitored using electromyography and TOF stimulation. MgSO4 caused rapid and profound recurarization in all 20 patients. MgSO4 decreased the amount of acetylcholine released at the motor nerve terminal and thus may lead to recurarization in patients previously exposed to neuromuscular blocking agent

Induction characteristics of 2% propofol in children

We have conducted a prospective, randomized study to evaluate the characteristics of induction of anaesthesia in children with 2% propofol. Children were allocated to receive propofol 3 mg kg-1 (group A), 4 mg kg-1 (group B) or 5 mg kg-1 (group C) of the 2% formulation. We observed a high incidence of spontaneous movements (90%) in group A and an incidence of coughing of 70% in group C. Induction in group B was characterized by a short induction time, low incidence of spontaneous movements (20%), pain on injection (10%) and excellent conditions for manual ventilatio