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Biomedical subjects

O H Wilder-Smith

Publications and source records attributed to O H Wilder-Smith.

At least 19 recordsLinked to original sources

Midazolam premedication reduces propofol dose requirements for multiple anesthetic endpoints.

PURPOSE: This study investigates the interactions between midazolam premedication and propofol infusion induction of anesthesia for multiple anesthetic endpoints including: loss of verbal contact (LVC; hypnotic), dropping an infusion flex (DF; motor), loss of reaction to painful stimulation (LRP; antinociceptive) and attainment of electroencephalographic burst suppression (BUR; EEG). METHODS: In a double blind, controlled, randomized and prospective study, 24 ASA I-II patients received either midazolam 0.05 mg x kg(-1) (PM; n = 13) or saline placebo (PO; n = 11) i.v. as premedication. Twenty minutes later, anesthesia was induced by propofol infusion at 30 mg x kg(-1) x hr(-1). ED50, ED95 and group medians for times and doses were determined and compared at multiple anesthetic endpoints. RESULTS: At the hypnotic, motor and EEG endpoints, midazolam premedication significantly and similarly reduced propofol ED50 (reduction: 18%, 13% and 20% respectively; P <0.05 vs unpremedicated patients) and ED95 (reduction: 20%, 11% and 20% respectively; P <0.05 vs unpremedicated patients). For antinociception (LRP), dose reduction by premedication was greater for propofol ED95 (reduction: 41%; P <0.05 vs unpremedicated patients) than ED50 (reduction: 18%; P <0.05 vs unpremedicated patients). Hemodynamic values were similar in both groups at the various endpoints. CONCLUSIONS: Midazolam premedication 20 min prior to induction of anesthesia reduces the propofol doses necessary to attain the multiple anesthetic endpoints studied without affecting hemodynamics in this otherwise healthy population. The interaction differs for different anesthetic endpoints (e.g., antinociception vs hypnosis) and propofol doses (e.g., ED50 vs ED95).

Adult↗

The management of chronic pain in Switzerland: a comparative survey of Swiss medical specialists treating chronic pain.

Chronic pain management by Swiss specialist physicians with the primary hypothesis that pain clinic practitioners conform better to good practice (interdisciplinarity, diagnostic/therapeutic routines, quality control, education) than other specialists treating chronic pain was surveyed. Management of all types of chronic pain by pain clinic practitioners and rheumatologists, oncologists or neurologists was compared via a mailed questionnaire survey (n=125/group). Two hundred and twenty-nine (46%) of 500 mailed questionnaires were returned with similar group return rates. Eighty-six percent of responders find chronic pain therapy very difficult/difficult; they estimate only 45% of these patients achieve good outcomes. Twenty-three per cent of responders belong to an interdisciplinary pain centre, but 72% of chronic pain patients are treated by responders alone. Fifty-nine percent never/only occasionally use therapeutic algorithms, 38% use formal pain diagnostic procedures, 20% have a pain quality control programme. Fifty-one percent lack past pain education, 37% do not attend continuing pain education, 69% agree that pain education is their greatest need. Pain clinic practitioners are more interdisciplinary and use more pain diagnostics than other specialists. They are matched by oncologists in education and success in therapeutic escalation, and bettered by them in algorithm use. Pain clinic practitioners and oncologists bring particular-differing-skills to chronic pain management compared to rheumatologists and neurologists. Chronic pain management diversity may result from differences in malignant and benign pain, and its generally being provided by the speciality treating the underlying cause. This survey identifies targets for improvement in areas fundamental to good chronic pain practice: interdisciplinarity, diagnostic/therapeutic tools, quality management and education.

Algorithms↗

Changes in sensory processing after surgical nociception.

Nociception results in peripheral and central changes in sensory processing. These changes are considered to significantly contribute to postoperative pain and its outcome. Objective measures of changes in sensory processing are now being studied in humans after surgery. Surgical nociception leads to both central excitation (eg, spinal sensitization) and central inhibition (eg, descending inhibition), with inhibition being the dominant response during the first day or so after surgery. Analgesia commenced before surgery (preemptive analgesia) depresses central sensitization and enhances central inhibition. Patients operated on under nonanalgesic anesthesia may exhibit rebound central sensitization for up to 5 days postoperatively after the cessation of postoperative opioid analgesia. There is only a weak relationship between the described objective changes in sensory processing after surgical nociception and subjective clinical pain measures such as pain intensity scales or postoperative analgesic consumption.

Humans↗

Analgesic action of i.v. morphine-6-glucuronide in healthy volunteers.

The pharmacodynamics of morphine-6-glucuronide (M-6-G) i.v. were assessed in 12 healthy male volunteers in an open study. After a single bolus dose of M-6-G 5 mg i.v., we measured antinociceptive effects, using electrical and cold pain tests, and plasma concentrations of M-6-G, morphine-3-glucuronide (M-3-G) and morphine. Pain intensities during electrical stimulation (at 30, 60 and 90 min after injection) and ice water immersion (at 60 min) decreased significantly (P < 0.005) compared with baseline. Mean plasma peak concentrations of M-6-G were 139.3 (SD 38.9) ng ml-1, measured at 15 min. Our data demonstrate that M-6-G has significant analgesic activity.

Adult↗

Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points.

We have studied the effects of midazolam premedication on multiple anaesthetic end-points (hypnotic, loss of verbal contact (LVC); motor, dropping an infusion flex or bag (DF); analgesic, loss of reaction to painful stimulation (LRP); and EEG, attainment of burst suppression (BUR)) during induction by slow thiopental infusion at a rate of 55 mg kg-1 h-1. Patients received midazolam 0.05 mg kg-1 i.v. (group TM, n = 12) or no midazolam (group T0, n = 13). ED50 and ED95 values and group medians for times and doses at the end-points were measured. Midazolam premedication reduced significantly thiopental ED50 and ED95 values at all end-points (exception for ED95 for BUR). Potentiation was greatest for the motor end-point (dropping the infusion bag (DF)) (ED95 +52%, ED50 +23%, median +39%), and smallest for painful stimulation (LRP) (median +18%; ED50 +13%). For LRP and DF, premedication was associated with significant, non-parallel increases in the slope of the thiopental dose-response curves, resulting in marked potency ratio changes from ED50 to ED95 (LRP +31%, DF +29%). There were no such increases for LVC or BUR. The interaction between midazolam and thiopental varied with the anaesthetic end-point and may also depend on the dose of thiopental. Our data suggest that the mechanism of interaction between midazolam premedication and thiopental was different for motor effects or analgesia (DF, LRP) compared with hypnotic effects or cortical depression (LVC, BUR), in agreement with the different central nervous system substrates underlying these distinct anaesthetic end-points.

Adult↗

Slow EEG-power spectra correlate with haemodynamic changes during laryngoscopy and intubation following induction with fentanyl or sufentanil.

We studied nociception-associated arousal following laryngoscopy and intubation in patients scheduled for elective open heart surgery, using EEG power spectra and hemodynamics. Either fentanyl (7 micrograms/kg; n = 30) or sufentanil (1 microgram/kg; n = 30) were given in a randomized fashion to induce anesthesia in heavily premedicated patients, followed by pancuronium bromide (100 micrograms/kg). EEG-power spectra (delta, theta, alpha, beta) as well as mean arterial blood pressure (MAP) and heart rate (HF) were measured at the following end-points: before the induction of anesthesia (control), 1 and 10 minutes after laryngoscopy and intubation (L & I). Linear regression analysis was computed to determine which of the EEG power spectra was most sensitive to detect insufficient blockade of nociceptive-related arousal when correlated with haemodynamics. In the fentanyl group the change in HF closely correlated with the decrease of power in the slow delta- and theta-domain (r2 = 0.98 and r2 = 0.89 respectively) of the EEG. The change in MAP also closely correlated with a decrease in the slow delta- and theta-domain (r2 = 0.97 and r2 = 0.99 respectively). There was little correlation in regard to spectral edge frequency (SEF) and HF and MAP changes (r2 = 0.36 and r2 = 0.12 respectively). In the sufentanil group the change in HF correlated closely with an increase of power in the fast alpha and a decrease in the slow theta-domain (r2 = 0.91 and r2 = 0.98 respectively) of the EEG. The changes in MAP closely correlated with an increase in the fast alpha-band a decrease in the slow theta-domain (r2 = 0.98 and r2 = 0.73 respectively). Also there was little correlation of SEF with HF and MAP changes (r2 = 0.09 and r2 = 0.02 respectively). Among the EEG-spectra, reduction of power in the slow delta- and theta-bands are the most sensitive parameters to determine insufficient antinociception of opioids commonly used for the induction in cardiac anesthesia. Increase of power in the alpha-band seems to be closely correlated with cortical reactivation and reduction of hypnosis, while a reduction of power especially in the deltabut more so in the theta-band of the EEG reflects nociception related arousal.

Alpha Rhythm↗

Sensory changes and pain after abdominal hysterectomy: a comparison of anesthetic supplementation with fentanyl versus magnesium or ketamine.

UNLABELLED: Drugs interacting with opioid or N-methyl-D-aspartate (NMDA) receptors may have differing effects on post-surgical sensory changes, such as central inhibition or spinal excitation. We compared the effect of supplementing isoflurane/N2O/O2 anesthesia with an opioid agonist (fentanyl [n = 15]) or two drugs inhibiting the NMDA system differently (magnesium, ketamine [n = 15 in each group]) on sensory changes after abdominal hysterectomy. Electric sensation, pain detection, and pain tolerance thresholds were determined (preoperatively and 1, 4, 24 h, and 5 days postoperatively) in arm, thoracic, incision, and leg dermatomes together with pain scores and cumulative morphine consumption. Thresholds relative to the arm were derived to unmask segmental sensory changes hidden by generalized changes. Absolute thresholds were increased 1-24 h, returning to baseline on Day 5, without overall differences among drugs. Fentanyl thresholds were lower 1 h and higher 5 days postoperatively compared with magnesium and ketamine; thresholds were lower at 24 h for magnesium versus ketamine. Relative thresholds increased compared with baseline only with fentanyl (1-4 h); none decreased. Pain scores and morphine consumption were similar. Thus, all adjuvants suppressed spinal sensitization after surgery. Fentanyl showed the most, and magnesium the least, central sensory inhibition up to 5 days postoperatively, with different patterns of inhibition directly postsurgery versus later. Differences in sensory processing were not reflected in clinical measures. IMPLICATIONS: We studied the effects on postsurgical sensory processing of general anesthesia supplemented by drugs affecting opioid or N-methyl-D-aspartate receptors using sensory thresholds. Generalized central sensory inhibition, differently affected by the drugs, predominated after surgery. All drugs suppressed spinal excitation. Clinical pain measures did not reflect sensory change.

Adult↗

Preoperative adjuvant epidural tramadol: the effect of different doses on postoperative analgesia and pain processing.

BACKGROUND: Tramadol is an analgesic with combined opioid agonist and monoamine reuptake blocker properties, which may be useful as a perioperative analgesic and antinociceptive adjuvant. METHODS: The dose-dependent effects of adjuvant preoperative epidural tramadol on postoperative analgesia (pain scores and patient-controlled analgesia (PCA) use) and pain processing (heat pain thresholds) were prospectively studied in a double-blind, randomised, placebo-controlled 5-day trial. Forty patients undergoing knee or hip surgery received anaesthesia with epidural lidocaine and epidural tramadol 20, 50 or 100 mg or placebo as a preoperative adjuvant. Postoperative analgesia was by intravenous PCA tramadol in all patients. RESULTS: Postoperative pain scores were similar in all groups. The time to first PCA use was shorter, the total dose and duration of PCA use greater, and side-effects more common with 20 mg tramadol than with 100 mg or placebo (P < 0.05). There were no differences in PCA doses required or side-effects between the tramadol 100 mg and placebo treatment groups. Heat pain tolerance thresholds were increased with 100 mg tramadol at 48 h postoperatively compared to baseline and placebo (P = 0.01). CONCLUSIONS: Preoperative adjuvant epidural tramadol does not improve postoperative analgesia after lidocaine epidural anaesthesia compared to placebo. Tramadol 20 mg results in anti-analgesia and increased side-effects. While tramadol 100 mg depresses postoperative pain-processing, as measured by heat pain tolerance thresholds, this is not reflected in improved clinical pain measures.

Analgesia, Epidural↗

No inhibition of gastro-intestinal propulsion after propofol- or propofol/ketamine-N2O/O2 anaesthesia. A comparison of gastro-caecal transit after isoflurane anaesthesia.

BACKGROUND: Gastrointestinal motility may be considerably reduced by anaesthesia and or surgery resulting in postoperative ileus. Inhibition of propulsive gut motility is especially marked after an opioid-based technique. Little, however, is known of the gastrointestinal effects of the hypnotic propofol when given continuously over a longer period of time, which is the case in total intravenous anaesthesia (TIVA) and in intensive care sedation. We therefore set out to study the effects of a propofol-based nitrous oxide/oxygen anaesthesia (group PO) on gastro-caecal transit time. The results were compared with a propofol-ketamine technique (group PK) and an isoflurane-based anaesthesia (group I; each group n = 20). METHODS: Gastro-caecal transit was determined by measurement of endexpiratory hydrogen concentration (ppm). Following gastral installation of lactulose at the end of the operation, the disaccharide was degraded by bacteria in the caecum, resulting in the liberation of hydrogen which was expired. A 100% increase in endexpiratory hydrogen concentration compared to the preinduction period was considered the end-point of gastro-caecal transit. RESULTS: There was no significant difference with regard to gastro-caecal transit in the three groups of patients. In the propofol group mean gastro-caecal transit was 119 (+/- 50.6 SD) min, in the propofol-ketamine group it was 147 (+/- 57.4 SD) min, and in the isoflurane group transit time was 122 (+/- 48.6 SD) min. CONCLUSION: The data suggest that propofol, even when given as a continuous infusion, does not alter gastrointestinal tract motility more than a standard isoflurane anaesthesia. The data may be particularly relevant to patients who are likely to develop postoperative ileus. They also suggest that in an ICU setting propofol does not alter gut motility more than a sedation technique with the analgesic ketamine.

Adult↗

Postoperative nausea and vomiting: a comparative survey of the attitudes, perceptions, and practice of Swiss anesthesiologists and surgeons.

Managing postoperative nausea and vomiting (PONV) depends on awareness of the problem, the therapeutic measures available, and effective implementation control systems. We mailed 616 PONV questionnaires to all 129 Swiss hospitals with anesthesiological and surgical departments. The responses [192 (31%) completed questionnaires from 87 (67%) hospitals] are representative of Swiss hospital anesthesiologists and surgeons. Anesthesiologists' perceptions of PONV are closer to those found in the literature than surgeons'. More than three quarters of anesthesiologists and less than half of surgeons practice PONV prophylaxis. Half of the respondents are dissatisfied with present antiemetics. Anesthesiologists worry about the cost of PONV prophylaxis, and surgeons are concerned about their lack of theoretical knowledge. Formal PONV policies are rare, with little consensus on treatment responsibilities. Sixty percent of respondents document PONV occurrence, and less than 20% perform any formal PONV audit. This survey identifies factors amenable to improvement regarding PONV management in Swiss hospitals. PONV education is a necessity, particularly for surgeons. Cost needs to be addressed with anesthesiologists. The limited therapeutic efficacy of antiemetics is a concern. PONV management needs standardization, organization, consensus, and research. Better audits and visibility in patients' charts could further improve the quality of PONV management.

Anesthesiology↗

Jugular venous bulb oxygen saturation monitoring in arteriovenous malformation surgery.

We describe a case in which jugular venous bulb oxygen saturation (SjvO2) monitoring proved useful during the surgical resection of an intracranial arteriovenous malformation (AVM). Surgical resection of large intracranial AVMs may be followed by normal perfusion pressure breakthrough with brain swelling, hyperemia, and subsequent problems in achieving hemostasis. SjvO2 monitoring during AVM embolization by interventional radiology has been shown to help in deciding whether embolization is sufficient to avoid such postresection hyperemia, but its use during surgical resection has not been described. In the case discussed, SjvO2 monitoring enabled assessment of the risk of postresection hyperemia preoperatively and permitted the degree and completeness of surgical AVM resection to be followed intraoperatively. During the normal perfusion pressure breakthrough bleeding which followed complete AVM resection, SjvO2 monitoring helped with safe management of the controlled hypotension that finally permitted hemostasis to be achieved.

Adult↗

Perioperative magnesium infusion and postoperative pain.

BACKGROUND: NMDA receptor activation is considered one of the mechanisms involved in postoperative pain and hypersensitivity. Magnesium is the physiological blocker of the NMDA-receptor-complex-associated calcium ionophore. The aim of this study was to determine if a pre-, intra- and postoperative infusion of magnesium would reduce postoperative pain. METHODS: In a prospective, randomised, double-blinded and placebo-controlled study, 24 patients undergoing elective hysterectomy in standardised general anaesthesia received a 5 h infusion of either placebo or magnesium laevulinate (initial bolus 8 mmol: then 8 mmol/h) starting with induction of anaesthesia. Postoperative analgesia was by PCA morphine for the first 48 h and patients were followed for 5 d with regular assessment of pain and side-effect scores. RESULTS: Overall, pain scores were similar with magnesium and placebo infusion, although patients in the magnesium group experienced more episodes of severe or unbearable pain (placebo = 6%, magnesium = 16%, P = 0.02). Median pain scores were higher in the magnesium group only at 3 h postoperatively (P = 0.04): afterwards there were no significant differences. Except for the first postoperative hour (placebo = 12.8 +/- 4.7 mg, magnesium = 9.3 +/- 3.2 mg, P = 0.04), cumulative morphine consumption was similar. Gastrointestinal complication rates and patient satisfaction were similar in both groups. CONCLUSIONS: Perioperative magnesium infusion does not improve postoperative analgesia. At the doses used in this study, the use of magnesium is associated with short-term decreases in postoperative analgesia.

Adult↗

Surgical pain is followed not only by spinal sensitization but also by supraspinal antinociception.

Nociception can produce segmental spinal sensitization or descending supraspinal antinociception. We assessed both types of sensory change after surgery during isoflurane-nitrous oxide anaesthesia with or without fentanyl before nociception. Patients undergoing back surgery received fentanyl 3 micrograms kg-1 (n = 15) or placebo (n = 15) before anaesthesia in a prospective, randomized, blinded study. Sensation, pain detection and tolerance thresholds to electrical stimulation were measured before operation at the arm, incision and herniated disc dermatomes (HDD) and 1, 2, 4, 6, 24 h and 5 days after operation, together with pain scores and patient-controlled morphine consumption (duration 24 h). For segmental effects, thresholds were normalized to the thresholds at a distant dermatome (arm). Raw pain thresholds were increased after operation (fentanyl > placebo) and were maximal at 4 h (pain tolerance in HDD: fentanyl +5.2 mA (+62.7%), placebo, +3.8 mA (+44.2%); P < 0.05 vs baseline for both). Normalized sensation thresholds decreased for placebo only (HDD/4 h: placebo, -1.8 (-44.8%), P < 0.05; fentanyl, +0.1 (+5.5%) ns). All changes returned to baseline by 24 h except for the placebo group normalized HDD sensation (d5: placebo, -2.4 (-59.7)%, P < 0.05; fentanyl -0.1 (-5.5%) ns). Pain scores and morphine consumption were similar. The study demonstrated both supraspinal analgesia and spinal sensitization after surgery. Fentanyl administration before operation augmented the former while decreasing the latter, and hence sensitization, especially if neuropathic, may particularly benefit from pre-emptive analgesia.

Adult↗

Doxacurium pharmacodynamics in children during volatile and opioid-based anaesthesia.

The interaction between doxacurium and halothane, isoflurane or alfentanil has not been studied in children. Using the cumulative dose-response technique and electromyography, we determined ED50 and ED90 of doxacurium during halothane (n = 9), isoflurane (n = 12) or alfentanil (n = 9) based anaesthesia in children aged 2-10 years. Both isoflurane and halothane potentiated the effects of doxacurium compared to alfentanil. The ED50 for doxacurium/halothane was 23.9 micrograms.kg-1 compared to 32.7 micrograms.kg-1 for doxacurium/alfentanil. The ED90 for doxacurium/isoflurane was 32.7 micrograms.kg-1 compared to 48.2 micrograms.kg-1 doxacurium/alfentanil (p < 0.05). There were no significant time course differences between the groups. When equipotent doses of doxacurium were used to provide muscle relaxation the duration of the neuromuscular block was similar in children who received aflentanil, halothane or isoflurane supplementation of N2O/O2 anaesthesia.

Alfentanil↗

Interaction of magnesium sulphate with vecuronium-induced neuromuscular block.

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 micrograms 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 sulphate. The ED50 and ED90 of vecuronium with MgSO4 were 25% lower than without MgSO4 (ED50: 21.3 vs 26.9 micrograms kg-1; ED90: 34.2 vs 45.7 micrograms kg-1; P < 0.05 for both). Mean onset time was 147.3 (SD 22.2) s in the MgSO4-vecuronium 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) min 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; P < 0.05). In the context of rapid sequence induction, pretreatment with MgSO4 improved the intubating score of vecuronium compared with vecuronium without MgSO4, reaching the same quality as that with suxamethonium 1 mg kg-1. We conclude that magnesium pretreatment increased the neuromuscular potency of vecuronium, in addition to modifying the time course of its neuromuscular block.

Adolescent↗