Henry P. Frizelle

The effects of intracuff lidocaine on endotracheal-tube-induced emergence phenomena after general anesthesia

UNLABELLED: Coughing during emergence from general anesthesia is a common clinical problem. We sought to determine whether inflating the endotracheal tube cuff with lidocaine would create a reservoir of local anesthetic, which might diffuse across the cuff membrane to anesthetize the mucosa, thus attenuating stimulation during extubation of the trachea. A total of 63 patients undergoing elective surgery were enrolled in a prospective, randomized, double-blinded study. After intubation of the trachea with an endotracheal tube, the cuff of the tube was inflated with either lidocaine 4%, saline, or air. After extubation, a blinded observer noted heart rate, blood pressure, oxygen saturation, end-tidal isoflurane concentration, and the incidence of coughing. Data were analyzed by using analysis of variance, Students t-test, and the chi(2) test for multiple variables. The groups were demographically comparable. There was no difference in hemodynamic or oxygen saturation data between either group. The incidence of coughing was decreased in the lidocaine group for the time period of 4-8 min postextubation (P < 0.05). We conclude that inflation of the cuff of the endotracheal tube can reduce the incidence of coughing in the initial postextubation period, a finding that may benefit certain patient groups in which this is particularly desirable. IMPLICATIONS: Tracheal intubation with an endotracheal tube is often necessary during anesthesia. After intubation, inflating a cuff around the endotracheal tube maintains a seal. This can result in coughing during emergence from anesthesia. Our study shows that inflating the cuff of an endotracheal tube with lidocaine rather than air can reduce the incidence of postextubation coughing.

A Comparison of Propofol with a Propofol-Ketamine Combination for Sedation During Spinal Anesthesia

Propofol (P) is increasingly used as a sedative during regional anesthesia.Providing titratable sedation and rapid recovery, it can compromise hemodynamic stability. However, in combination with ketamine (K), it provides stable hemodynamics during total intravenous anesthesia, avoiding emergence phenomena. We compared the efficacy, respiratory and hemodynamic profiles, and side effects of these two sedative regimes in patients undergoing spinal anesthesia. Forty patients, ASA physical status I and II, undergoing urologic or orthopedic procedures were randomly assigned to one of two groups (n = 20 each). Group 1 (P + K) received initial doses of 0.4 mg/kg P, 0.1 mg/kg K, followed by an intravenous infusion of 1.2 mg [centered dot] kg-1 [centered dot] h-1 and 0.3 mg [centered dot] kg-1 [centered dot] h-1, respectively. Group 2 (P) received bolus 0.5 mg/kg and infusion 1.5 mg [centered dot] kg-1 [centered dot] h-1. Subsequent infusion rates were titrated to a predetermined sedation level using a 5-point score. Heart rate, arterial pressure, respiratory rate, oxygen saturation end-tidal CO2, and oxygen requirements were recorded. Sedation scores were similar for both groups. There was no difference in total propofol requirements between Group 1 (146 +/- 94 mg) and Group 2 (137 +/- 52 mg) (mean +/- SD). Mean arterial pressure was significantly higher in the P + K group, e.g., 91 mm Hg (86-94) vs 75 mm Hg (69-83) at 30 min (mean +/- SD). Administration of vasopressors and fluids as well as recovery and emergence phenomena were similar between groups. Although the described additive effect of propofol and ketamine was not confirmed, the combination conferred hemodynamic stability during spinal anesthesia. (Anesth Analg 1997;84:1318-22)

Fentanyl and clonidine as adjunctive analgesics with levobupivacaine in paravertebral analgesia for breast surgery

The addition of fentanyl or clonidine to levobupivacaine was evaluated in patients undergoing breast surgery under general anaesthesia with intra‐ and postoperative paravertebral analgesia. Patients were randomly allocated to four groups: Group L received 19 ml bolus levobupivacaine 0.25% plus 1 ml saline followed by an infusion of levobupivacaine 0.1%; Group LF received 19 ml bolus levobupivacaine 0.25% plus fentanyl 50 μg followed by an infusion of levobupivacaine 0.05% with fentanyl 4 μg.ml−1; Group LC received 19 ml bolus levobupivacaine 0.25% plus clonidine 150 μg followed by an infusion of levobupivacaine 0.05% with clonidine 3 μg.ml−1; Group C (control) received general anaesthesia without paravertebral analgesia. All groups received postoperative i.v. morphine patient controlled analgesia (PCA). Although mean (SD) postoperative PCA morphine consumption was decreased in LF [7.9 (4.1) mg] and LC [5.9 (3.5) mg]vs L [27.7 (8.6) mg] or C patients [21.7 (5.5) mg], p < 0.01, paravertebral fentanyl and clonidine were associated with significantly increased vomiting and hypotension, respectively.

The effect of passive smoking on the incidence of airway complications in children undergoing general anaesthesia.

The aim of this study was to assess whether passive smoking affected the frequency of airway complications in children undergoing general anaesthesia. One hundred and twenty‐five children undergoing general anaesthesia for elective daycase surgery were monitored for adverse respiratory events and desaturation during induction, intra‐operatively and in the recovery room. Oxygen saturation was monitored throughout and a venous sample was taken for estimation of carboxyhaemoglobin levels. Parents were asked to fill in a questionnaire detailing their smoking habits. Sixty‐three of the children were passive smokers with a potential daily exposure varying from 5–130 cigarettes. There was no difference in the frequency of respiratory events between passive smokers and those not exposed to cigarette smoke at induction or intra‐operatively. However, in the recovery room, desaturation was significantly more common in passive smokers (p<0.02). This was related to the cumulative number of cigarettes smoked by individuals to whom the child was exposed (p<0.05). Neither carboxyhaemoglobin levels nor domiciliary address were predictive of desaturation. This study suggests that passive smoking contributes to postoperative arterial oxygen desaturation following general anaesthesia in children.

Pharmacokinetics of levobupivacaine, fentanyl, and clonidine after administration in thoracic paravertebral analgesia.

Background and Objectives: There is little knowledge of the pharmacokinetics of local anesthetics and adjunctive analgesics after paravertebral blockade. We evaluated the pharmacokinetics of low-dose levobupivacaine, fentanyl, and clonidine after paravertebral analgesia for breast surgery. Methods: Thirty-eight patients receiving paravertebral analgesia for breast surgery received a 19-mL paravertebral bolus of levobupivacaine 0.25% combined with a 1-mL volume of saline (group L, 13 patients), fentanyl 50 &mgr;g (group LF, 13 patients), or clonidine 150 &mgr;g (group LC, 12 patients) followed 1 hour later by infusion of levobupivacaine 0.1% (L), levobupivacaine 0.05% with fentanyl 4 &mgr;g/mL (LF), or levobupivacaine 0.05% with clonidine 3 &mgr;g/mL (LC), respectively. Plasma concentrations of study drugs were determined at intervals up to 24 hours after bolus injection. Results: There was rapid absorption of levobupivacaine after bolus with mean (standard deviation) maximum plasma concentration (Cpmax) of 0.51(0.24) &mgr;g/mL in a median time to maximum concentration tCpmax of 15 minutes. Mean Cpmax fentanyl and clonidine after bolus were 0.62 (0.37) and 0.79 (0.23) ng/mL, in a median tCpmax of 15 and 22.5 minutes, respectively. Mean Cpmax levobupivacaine after infusion was 0.47 (0.41) &mgr;g/mL in a median tCpmax of 24 hours. There was progressive accumulation of fentanyl and clonidine at 24 hours with a mean Cpmax of 0.72 (0.33) and 1.74 (0.70) ng/mL, respectively. Conclusions: After paravertebral bolus and infusion administration, Cpmax levobupivacaine was within the safe range. Cpmax fentanyl and clonidine were less than the effective levels after IV administration, suggesting that their analgesic effect may be partly attributed to a peripheral mechanism of action.

A comparison of the effects on bispectral index of mild vs. moderate hypothermia during cardiopulmonary bypass

Background and objective: Bispectral Index® correlates with depth of hypnosis in adult patients. Bispectral index monitoring has been separately examined and validated during both mild and moderate hypothermic cardiopulmonary bypass. However, the effect on bispectral index of these two differing cardiopulmonary bypass temperature regimes has not previously been compared, particularly with the use of volatile anaesthetic agents. Methods: Following Institutional Ethics Committee approval and informed consent, 30 patients undergoing coronary artery bypass grafting had additional bispectral index monitoring. Sixteen patients had mild hypothermic bypass (32–34°C), and 14 had moderate hypothermic bypass (28–30°C). Anaesthesia was standardized, and was maintained with enflurane throughout surgery. Scores were recorded at 14 specific event‐related time points during surgery. Results: This study has demonstrated that in this adult population, a relationship exists between bispectral index score and temperature throughout the duration of cardiac surgery, which included mild or moderate hypothermic cardiopulmonary bypass. It also demonstrated that patients which were categorized as having received moderately hypothermic cardiopulmonary bypass had lower bispectral index scores than those patients who received mild hypothermic cardiopulmonary bypass, at time points corresponding approximately with median steady‐state bypass temperature, pre‐re‐warming and early re‐warming periods. Conclusions: Moderate hypothermic cardiopulmonary bypass has lower bispectral index scores when compared to mild hypothermic cardiopulmonary bypass, at a steady state of inspired enflurane. This may reflect an actual increase in the depth of hypnosis. However, as this study did not address the physico‐chemical changes of the volatile agent or the accuracy of the bispectral index algorithm at lower temperatures, we would not advocate a change in practice based solely on this report.

The combined effects of halothane and lamotrigine on excitatory postsynaptic potentials and use-dependent block in the rat dentate gyrus in vitro

UNLABELLED Halothane affects synaptic transmission in the rat hippocampus with a 50% effective dose (ED50) correlating with clinical figures for minimum alveolar anesthetic concentration (MAC). Halothane dose-dependently suppresses glutamate receptor-mediated excitatory postsynaptic potentials (EPSPs) in the rat hippocampus. It also inhibits voltage-gated Na+ channels. The anticonvulsant lamotrigine acts as a Na+ channel antagonist and inhibits glutamate release after Na+ channel activation. Given their known similar sites of action, the combination of halothane and lamotrigine may alter the inhibition produced by either drug alone. Extracellular recordings of field EPSPs were obtained from the dentate gyrus in the presence of 100 microM picrotoxin (to block GABAA receptors). Stimulation at 30 Hz (200 ms, pulse duration 0.1 ms, six pulses) allowed us to investigate use-dependent block (UDB). Once a stable equilibrium was established, halothane and lamotrigine were administered via the perfusate, and recordings were collected. Both halothane (n = 12) and lamotrigine (n = 6) exhibited reversible inhibition of the EPSP (ED50 0.28 mM [1.2%] and 100 microM, respectively) at low-frequency stimulation. Slices (n = 6) exposed to halothane 0.2 mM (0.75%), then to lamotrigine, showed reduced sensitivity compared with lamotrigine alone. Halothane 0.2 mM potentiated the control UDB (Pulse 6:31% +/- 11% control versus 20.5% +/- 2.5% halothane 0.75%; P < 0.05; n = 6). Lamotrigine had no effect on control UDB. The combination (n = 6) did not alter UDB effects compared with controls or lamotrigine alone. Halothane may reduce the effect of lamotrigine on glutamate release, either at the receptor or via effects at the inactivated Na+ channel. The site of interaction requires further examination. IMPLICATIONS The general and local anesthetic drugs halothane and lamotrigine act at both the glutamate receptor and the Na+ channels and, in our experiments, independently inhibited synaptic transmission at low-frequency stimulation. Although halothane potentiated control use-dependent block, lamotrigine had no effect. Halothane attenuated the inhibitory dose-dependent effects of lamotrigine on synaptic transmission at a low frequency. The clinical importance of this interaction in patients presenting for anesthesia remains unanswered.

Effects of the combination of halothane and serotonin uptake blockers on synaptic transmission in the rat dentate gyrus in vitro.

Although the exact basis of their action remains unknown, volatile agents affect noradrenergic and serotoninergic systems. Imipramine and fluoxetine have documented effects on these neurotransmitter transmission systems. Given the common sites of action of these antidepressants and halothane, we examined their individual and combined effects on tonic excitatory post-synaptic potentials (EPSPs) and frequency dependent blockade in the rat dentate gyrus in vitro. Extracellular recordings of field EPSPs were maintained from the dentate gyrus, in the presence of picrotoxin (100 microM). Stimulation at 30 Hz (200 ms) allowed investigation of frequency dependent blockade. Once a stable equilibrium was established, halothane, imipramine and fluoxetine were administered via the perfusate and recordings were made. Halothane produced a dose dependent reduction in EPSP amplitude (EC50 0.28 mM; n = 12). Imipramine (1-10 microM) potentiated the EPSP amplitude (148.2 +/- 8.2%; imipramine 1 microM; n = 6). Fluoxetine (0.5-10 microM) reduced EPSP amplitude to 83.7 +/- 22.1% of control (n = 6). In the presence of halothane 0.2 mM, imipramine reduced the EPSP amplitude to 56.5 +/- 9.9% of control (imipramine 10 microM; n = 6; p < 0.05 compared with imipramine alone). Halothane (0.2 mM) demonstrated frequency dependent blockade. However, neither imipramine nor fluoxetine showed use dependent inhibition at the doses investigated. When combined with halothane 0.2 mM, fluoxetine 10 microM demonstrated frequency dependent blockade at the sixth pulse in the train compared with controls (13.8 +/- 4.7% vs 38.1 +/- 8.3%; n = 6; p < 0.05). The halothane-imipramine combination did not exhibit use dependent blockade greater than controls. The reversal of imipramine-induced EPSP potentiation by the preapplication of halothane has not been previously reported. It may be due to modulation of noradrenergic transmission by halothane. The frequency dependent blockade produced by the combination of fluoxetine 10 microM and halothane may be mediated by a nonspecific membrane effect on 5-HT uptake. These differing effects underline the broad action of volatile agents on synaptic mechanisms.

Intrathecal narcotics in cancer pain - a case report

SummaryA 61 year old female patient presented with metastatic bone pain three years post mastectomy. Standard oral analgesics and epidural morphine were ineffective in achieving pain control. Her pain was eventually controlled with morphine sulphate 48 mg daily via a self administered intrathecal pump. These devices are being used with increasing frequency and this case report highlights some of the problems encountered in this patient’s management.