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J W Sear

Publications and source records attributed to J W Sear.

At least 37 records · Page 2Linked to original sources

Anaesthesia and isolated systolic hypertension--pathophysiology and anaesthesia risk.

This review examines the pathophysiology of isolated systolic hypertension, changing medical perspectives on this condition as a cardiovascular risk factor in the community and evolving evidence of it being an independent risk factor for perioperative morbidity and mortality. Hypertension is regarded as an added risk in anaesthesia. Continuation of antihypertensive medication through the perioperative period is an established principle. Studies supporting this practice have demonstrated greater perioperative haemodynamic stability in association with general anaesthesia and surgery in patients with treated hypertension compared to untreated hypertension. Therapy has historically focused on control of diastolic blood pressure, rather than systolic blood pressure. Recent clinical trial data and data from large observational studies show a closer association of systolic hypertension with both coronary heart disease and stroke compared with diastolic hypertension. This has led to recommendations for aggressive treatment of isolated systolic hypertension, especially in patients over 65 years old. The association between decreased compliance of the central systemic arteries and isolated systolic hypertension is well understood. The fact that this same pathology, lack of compliance of central arteries, can cause a decrease in diastolic blood pressure is not so well recognised. This means that, in patients with isolated systolic hypertension, decreasing diastolic blood pressure can be associated with worsening arterial disease and that systolic minus diastolic blood pressure may give a better indication of the problem. Anaesthetic assessment and technique should be studied and potentially revised in the light of these changes in perspective on isolated systolic hypertension.

Adult↗

Can molecular similarity-activity models for intravenous general anaesthetics help explain their mechanism of action?

BACKGROUND: The importance of molecular shape and electrostatic potential in determining the activities of 11 structurally-diverse i.v. general anaesthetics was investigated using computational chemistry techniques. METHODS: The free plasma anaesthetic concentrations that abolished the response to noxious stimulation were obtained from the literature. The similarities in the molecular shapes and electrostatic potentials of the agents to eltanolone (the most potent anaesthetic agent in the group) were calculated using Carbo indices, and correlated with in vivo potency. RESULTS: The best model obtained was based on the similarities of the anaesthetics to two eltanolone conformers (r2=0.820). This model correctly predicted the potencies of the R- and S-enantiomers of ketamine, but identified alphaxalone as an outlier. Exclusion of alphaxalone substantially improved the activity correlation (r2=0.972). A bench mark model based on octanol/water partition coefficients (r2=0.647) failed to predict the potency order of the ketamine enantiomers. CONCLUSIONS: The results demonstrate that a single activity model can be formulated for chiral and non-chiral i.v. anaesthetic agents using molecular similarity indices.

Anesthesia, Intravenous↗

Peri-operative silent myocardial ischaemia and long-term adverse outcomes in non-cardiac surgical patients.

Two hundred and seventy-five non-cardiac surgical patients were recruited to determine risk factors associated with the development of postoperative cardiovascular complications during the first year after surgery. Patients underwent ambulatory electrocardiography pre- and postoperatively. There were 34 adverse events over the whole study period. Twenty-four occurred within 6 months and the remaining 10 occurred between 6 and 12 months postoperatively. Silent myocardial ischaemia was associated with adverse outcome over both the first 6 months [OR 4.44 (95% CI 1.77-11.13)] and the whole study period [OR 2.81 (1.26-6.07)]. Other risk factors were: vascular surgery [OR 17.09 (2.67-351.44)], history of angina [OR 6.29 (2.21-17.62)], concurrent treatment with calcium entry blockers [OR 2.68 (1.03-6.93)] and smoking [OR 4.93 (2.00-12.02)]. None of these was a useful predictor of long-term outcome (between 6 and 12 months postsurgery). These results are at variance with other published data, but we conclude that monitoring for peri-operative silent myocardial ischaemia does not aid the prediction of long-term cardiovascular complications.

Adult↗

Morphine, pethidine and buprenorphine disposition in the cat.

Pharmacokinetics of morphine, buprenorphine and pethidine were determined in 10 cats. Six cats received morphine (0.2 mg/kg) intravenously and four intramuscularly. Five received buprenorphine (0.01 mg/kg) intravenously and six intramuscularly. Six received pethidine (5 mg/kg) intramuscularly. Jugular venous blood samples were collected at time points to 24 h, and plasma morphine concentrations were measured by high performance liquid chromatograpy (HPLC), buprenorphine by radioimmunoassay (RIA) and pethidine by gas chromatography. Our data for morphine show elimination half-life (t1/2el) 76.3 min intravenous (i.v.) and 93.6 min intramuscular (i.m.); mean residence time (MRT) 105.0 and 120.5 min; clearance (Clp) 24.1 and 13.9 mL/kg/min; and volume of distribution (V(dss)) 2.6 and 1.7 L/kg, respectively. Comparable data for buprenorphine are t1/2el 416.8 and 380.2 min; MRT 417.6 and 409.8 min; Clp 16.7 and 23.7 mL/kg/min; and V(dss) 7.1 and 8.9 L/kg. For i.m. pethidine, t1/2el 216.4 min; MRT 307.5 min; Clp 20.8 mL/kg/min and V(dss) 5.2 L/kg. For i.m. dosing, the tmax for morphine, buprenorphine and pethidine were 15, 3 and 10 min, respectively. The pharmacokinetics of the three opioids in cats are broadly comparable with those of the dog, although there is a suggestion that the cat may clear morphine more slowly.

Analgesics, Opioid↗

Intercurrent drug therapy and perioperative cardiovascular mortality in elective and urgent/emergency surgical patientst.

The Oxford Record Linkage Study (ORLS; an epidemiological database) was used to examine relationships between intercurrent cardiovascular drug therapy and cardiac death within 30 days of elective or emergency/urgent surgery under general anaesthesia. Cases identified from the ORLS were paired with matched control patients. Clinical details were obtained from the patients' medical notes. In elective surgical patients, there was no effect of beta-adrenoceptor or calcium entry channel blockade, diuretics or digoxin on cardiac death after adjusting for confounding variables. Use of nitrates was associated with an odds ratio of 4.79 [95% confidence interval (CI) 1.01-22.72] for cardiac death after adjustment for confounding by a history of angina and residual age difference. In emergency/urgent patients, there were significant univariate associations with cardiac death for intercurrent use of angiotensin converting enzyme (ACE) inhibitors (odds ratio 1.18) and diuretics (odds ratio 4.95; 95% CI 1.82-13.46). However, neither maintained significance after adjustment for the confounding effect of cardiac failure. We conclude that, with the possible exception of the use of nitrates in elective surgical patients, chronic intercurrent drug treatment alone does not significantly affect the odds of cardiac death within 30 days of surgery.

Adrenergic beta-Antagonists↗

Increases in serum concentrations of cardiac proteins and the prediction of early postoperative cardiovascular complications in noncardiac surgery patients.

We investigated the use of measurements of serum concentrations of the cardiac proteins troponins I and T as biochemical markers of myocardial cell damage in 80 patients undergoing vascular or major orthopaedic surgery. Holter electrocardiographic monitoring was carried out before surgery and for 3 days after surgery. Blood samples for troponins I and T and creatine kinase-MB isoenzyme were taken on each of these 4 days. Outcome was assessed at 3 months using a patient questionnaire, general practitioner follow-up and case notes review. Silent postoperative myocardial ischaemia was detected in 21 patients; increases in troponins I and T and creatine kinase-MB occurred in four, six and 17 of these patients, respectively. Eight patients suffered major postoperative complications (cardiac death, myocardial ischaemia, congestive cardiac failure, unstable angina and cerebrovascular accident) and 21 minor complications (poorly controlled hypertension needing increased or new additional treatment, palpitations, increased tiredness or shortness of breath in the absence of known respiratory disease). There were no associations between postoperative ischaemia and cardiac protein concentrations. The relative odds for the associations of major adverse outcome at 3 months after surgery and postoperative ischaemia or increased serum concentrations of the three proteins were 5.39 [95% confidence intervals 1.16-27.67] for postoperative ischaemia; 5.64 [1.07-31.00] for creatine kinase-MB isoenzyme; 17.00 [2.20-116.54] for troponin T and 13.20 [1.12-135.00] for troponin I. We found troponin T to be the only prospective marker for both major and minor cardiovascular complications (relative odds 10.65 [1.26-252.88]).

Aged↗

Effect of chronic intercurrent medication with beta-adrenoceptor blockade or calcium channel entry blockade on postoperative silent myocardial ischaemia.

We have examined observational data from four published studies investigating the incidence of postoperative silent myocardial ischaemia (post-SMI) for the effects of chronic intercurrent therapy with beta-adrenoceptor blockade or chronic calcium channel entry blockade. A total of 453 patients underwent ambulatory ECG monitoring before and for 2 days after non-cardiac surgery; 79 patients were receiving chronic intercurrent beta-adrenoceptor blockade and 70 calcium channel entry blockade for ischaemic heart disease or arterial hypertension. Using logistic regression analysis, we defined a model for post-SMI that included four significant terms: beta-adrenoceptor blockade; calcium channel entry blockade; arterial hypertension; and vascular surgery. Using univariate regression, there was no effect of chronic beta-adrenoceptor blocking therapy on post-SMI (odds ratio 0.94 (95% confidence intervals 0.54-1.65)), but there was a higher incidence of post-SMI in patients receiving chronic calcium channel entry blocking drugs (odds ratio 1.95 (1.15-3.32); P = 0.015). There was no interaction between beta-adrenoceptor blockade and calcium channel entry blockade for postoperative SMI (odds ratio 2.48 (0.71-8.73)), but there was an interaction between beta-adrenoceptor blockade, calcium channel entry blockade, hypertension and vascular surgery (P = 0.0201). These findings are at variance with those which have shown effects of preoperative beta-adrenoceptor blockade on the incidence of post-SMI over the first 7 days after operation, and on mortality rates to 2 yr. There are no comparable data examining the effects of chronic intercurrent calcium channel entry blockade.

Adrenergic beta-Antagonists↗

Peri-operative silent myocardial ischaemia in patients undergoing lower limb joint replacement surgery: an indicator of postoperative morbidity or mortality?

One hundred and twenty-seven patients undergoing major lower limb joint replacement surgery were studied to determine the incidence of silent myocardial ischemia and to ascertain any link between pre-operative cardiac risk factors, silent myocardial ischaemia and postoperative morbidity. Patients underwent ambulatory ECG monitoring for 4 days (on the pre-operative night and for 3 days postoperatively). Postoperative cardiorespiratory symptomatology and morbidity was assessed by questionnaire at 3 months. Eighty-seven patients had risk factors for silent myocardial ischaemia; 42 patients (30 with risk factors) had peri-operative silent myocardial ischaemia. The median ischaemic loads (range) were 1.04 (0.32-13.31) min.h-1 pre-operatively and 5.53 (0.26-56.39), 6.69 (0.04-42.71) and 1.23 (0.1-53.74) min.h-1 on postoperative days 1-3, respectively. Risk factors did not predict the occurrence of silent myocardial ischaemia or an increased ischaemic load pre-operatively or overall postoperatively. New symptoms (chest pain, palpitations, breathlessness or fatigue) were associated with both silent myocardial ischaemia and ischaemic load (p < 0.05). Thus cardiac risk factors do not predict the occurrence of silent myocardial ischaemia or adverse outcome. Peri-operative silent myocardial ischaemia was associated with increased postoperative fatigue.

Aged↗

Risk factors for cardiovascular death within 30 days after anaesthesia and urgent or emergency surgery: a nested case-control study.

The Oxford Record Linkage Study (an epidemiological database) was used to identify patients who died from a cardiovascular cause within 30 days of emergency or urgent surgery under general anaesthesia. Each case was paired with a control patient (matched for age within 10 yr of the patient, operation and consultant). Additional clinical information was sought from the patient's case notes. Cases and controls were compared for cardiovascular risk factors using conditional logistic regression analysis and a prognostic model was generated. Only one significant risk factor was identified in the final model: a history of cardiac failure (odds ratio 14.84; 95% confidence intervals 2.53-87.13; P = 0.003). Associations between a history of cerebrovascular accident or renal impairment and cardiovascular mortality were seen using univariate analysis but not after adjustment for confounding factors.

Adult↗

Risk factors for cardiovascular death after elective surgery under general anaesthesia.

A large epidemiological data set was used to identify 115 patients who died from a cardiovascular cause within 30 days of elective surgery under general anaesthesia. For each patient, a control was identified, matched for age (within 5 yr of the patient), sex, operation and consultant. Patients and controls were compared for cardiovascular risk factors in a matched analysis using conditional logistic regression, and a prognostic model was generated. Three risk factors were included in the final model: previous myocardial infarction (odds ratio 3.18 (95% confidence intervals (CI) 1.22-8.28), P = 0.018), history of hypertension (odds ratio 1.90 (0.99-3.62), P = 0.047) and renal failure (odds ratio 3.56 (1.04-12.10), P = 0.043).

Adult↗

New induction agents.

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Anesthetics, Intravenous↗

Predictors of postoperative myocardial ischaemia. The role of intercurrent arterial hypertension and other cardiovascular risk factors.

One hundred and eighty-three patients were studied to examine the role of a number of risk factors in the development of silent ischaemia after general anaesthesia for general and vascular surgery. We collected evidence of cardiovascular risk factors using a binary questionnaire. The patients were monitored pre- and postoperatively using a Holter ECG monitor. Usable data were collected on 140 patients. Pre-operative silent myocardial ischaemia was found to be strongly associated with postoperative silent myocardial ischaemia (odds ratio: 10.8, 95% confidence intervals: 3.8-30.7). A history of hypertension, indicated by treatment with antihypertensive drugs, was associated with increased risk (odds ratio: 2.58, 95% confidence intervals: 1.12-5.96). A linear trend was found for risk associated with increasing admission systolic blood pressure (odds ratio: 1.20 for each 10-mmHg increase in systolic pressure, 95% confidence intervals: 1.01-1.42). An association between vascular surgery and postoperative silent myocardial ischaemia was also confirmed (odds ratio: 2.36, 95% confidence intervals: 1.1-5.1).

Adult↗