J. W. Sear

Myocardial ischemia in untreated hypertensive patients: effect of a single small oral dose of a beta-adrenergic blocking agent

In a non-double-blind, prospective, randomized study, the intraoperative electrocardiograms of 128 mildly hypertensive surgical patients were examined in order to determine the incidence of myocardial ischemia during anesthesia. No patient had been receiving chronic antihypertensive therapy prior to the study, but a single small oral dose of a beat-adrenergic blocking agent (labetalol, atenolol, or oxprenolol) was given to 89 of them along with premedication-Forty-four per cent of the untreated control patients and 61% of the patients pretreated with a beat-adrenergic blocking agent had normal preoperative electroca rdiograms and no risk factors for coronary artery disease other than hypertension (this difference between groups was not statistically significant). During tracheal intubation and/or emergence from anesthesia, a brief, self-limited episode of myocardial ischemia was detected in 11 of 39 untreated control patients, and in two of 89 patients pretreated with a betaadrenergic blocking agent (P < 0.001). Tachycardia always accompanied the ischemic events, but a conspicuous increase in blood pressure did not. The authors conclude that mild hypertension, when untereated prior to the induction of anesthesia, is associated with a high incidence of myocardial ischemia; and that a single small oral dose of a beat-adrenergic blocking agent, given with premedication, can significantly reduce that risk.

RENAL FAILURE AND THE USE OF MORPHINE IN INTENSIVE CARE

Intravenous morphine infusions were given to 20 patients in the intensive-care unit to provide sedation and analgesia. In 10 of the patients renal impairment was already present or developed during intensive care. Plasma morphine concentrations for a given dose of morphine and morphine clearance depended on renal function; dose-related plasma morphine concentrations rose as renal function deteriorated. Reduced morphine clearance leads to increased elimination half-life of the drug, and neurological impairment caused by unrecognised high concentrations of morphine could result in an incorrect diagnosis of cerebral damage in patients in intensive care.

Hemodynamic and Hepatic Effects of Methohexital Infusion during Nitrous Oxide Anesthesia in Humans

The hemodynamic effects of methohexital, at infusion rates of 60—65 and 120 μg/kg/min with concomitant inhalation of 67% nitrous oxide in oxygen, have been studied during spontaneous and controlled ventilation in 8 patients. Under most of the conditions studied methohexital infusion anesthesia was associated with lower arterial pressure (−13% to −33%) than in the awake state, decreased cardiac output (−26% to −38%), and increased systemic vascular resistance (+ 5% to +37%) during surgery, but also with decreased cardiac output (−25%) and decreased systemic vascular resistance (−13%) during anesthesia without surgery. The higher infusion rate was not associated with decreases in arterial pressure or cardiac output during either spontaneous or controlled ventilation. The hemodynamic response to laryngoscopy and intubation was poorly suppressed by methohexital in that peak arterial pressures exceeded the preanesthetic values by 33%. No evidence of impaired hepatocellular function was found after infusions of methohexital lasting up to 4 h.

Impact of prolonged elevated heart rate on incidence of major cardiac events in critically ill patients with a high risk of cardiac complications

Objective:To assess the incidence of major cardiac events in critically ill patients with a high risk of cardiac complications presenting with an elevated heart rate. Design and Setting:Observational, retrospective study in a 15-bed medical/surgical Intensive Care Unit (ICU) at a university hospital for a period of 12 months. Patients:We studied patients with a high risk of cardiac complications, according to the revised Goldman index, who were treated for at least 36 hrs in the ICU. Patients presenting with prolonged elevated heart rate, defined as a heart rate >95 beats/min for >12 hrs in at least one 24-hr period of their ICU stay, were investigated. Cardiac high-risk patients not developing this criterion served as controls. Major cardiac events, defined as nonfatal myocardial infarction, nonfatal cardiac arrest, and cardiac related death, were the primary outcome measures. Results:From a total of 791 patients, 69 patients were assessed as cardiac high-risk patients. Of 39 patients with prolonged elevated heart rates, 19 (49%) sustained major cardiac events, whereas in the control group of 30 patients, only four patients (13%) had a major cardiac event (p = .002; odds ratio, 6.2). Patients with elevated heart rate had to be treated 4.5 days longer in the ICU (p = .01), whereas the ICU and 30-day post-ICU discharge survival rates did not differ significantly. Conclusions:In this study, we provide evidence for an increased incidence of major cardiac events in critically ill, cardiac high-risk patients with a prolonged elevated heart rate during their ICU stay. In addition, elevated heart rate was associated with a significantly longer ICU stay.

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).

Peri-operative endocrine effects of etomidate

This study investigated the effects of etomidate on endocrine responses to anaesthesia and surgery. Patients undergoing abdominal hysterectomy received standard anaesthetics of either etomidate for induction with etomidate infusion, or thiopentone and halo thane. Etomidate suppressed the secretion of cortisol and aldosterone for between 8 and 22 hours after the end of the etomidate infusion; 11‐deoxycortisol secretion was not suppressed during the etomidate infusion, but rose postoperatively; 17α‐hydroxyprogesterone suppression also lasted only as long as the etomidate infiion. There were no effects on plasma oestradiol, A CTH, or prolactin, but growth hormone concentrations were elevated in the etomidate group. Etomidate was concluded to have influenced adrenocortical function only, where it probably inhibits 11 β‐hydroxylation, 17 α‐hydroxylation and other intramitochondrial hydroxylation reactions. There were no clinical sequelae attributable to adrenocortical suppression. The relationship of chemical structure of etomidate and other phenylated imidazoles to inhibition of steroidogenesis is discussed.

Statin therapy: a potentially useful peri-operative intervention in patients with cardiovascular disease

Statin cardiovascular protection is mediated by lipid lowering and pleiotropic effects. The efficacy of statins has been established in non‐surgical patients with cardiovascular disease and also more recently in non‐surgical patients who sustain an acute coronary event. Peri‐operative statin administration has been shown to improve both short‐term and long‐term cardiac outcome following non‐cardiac and coronary bypass graft surgery. This cardioprotection may be independent of peri‐operative haemodynamics due to a positive effect on plaque stability. Recommendations for the peri‐operative statin administration are suggested. These include indications for peri‐operative statin therapy, timing of administration, therapeutic targets, duration of administration, the adverse implications of peri‐operative statin withdrawal, safety and cost‐effectiveness.

Issues in the Perioperative Management of the Elderly Patient with Cardiovascular Disease

The elderly patient may show normal physiological changes of the cardiovascular and respiratory systems that accompany aging, as well as features of intrinsic cardiac disease. The latter include: a past history of myocardial infarction or ischaemic heart disease; history of congestive cardiac failure; angina; arterial hypertension (BP >140/90mm Hg); and conduction disorders. A key aspect to the safe and effective anaesthetic management of the elderly patient with cardiac disease is a careful preoperative assessment and optimisation of pre-existing drug therapies. All cardiac medications should be continued up to and including the morning of surgery with the exception of anticoagulation involving warfarin, and perhaps large doses of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists in patients with hypertension or heart failure.Anaesthetic techniques used in these patients should avoid episodes of excessive hypotension after induction of anaesthesia or large blood loss, or the combination of hypertension and tachycardia after noxious stimulation. The latter physiological disturbances are pivotal for the development of myocardial ischaemia.Both premedication (if used) and anaesthesia should avoid excessive sedation and respiratory depression. The choice of anaesthetic technique may vary between: a balanced technique involving an opiate and a volatile agent; an intravenous technique utilising infusions of propofol; or regional anaesthesia with or without additional sedation. There are no good data to suggest any one technique is better than the rest.The occurrence of ischaemia in the perioperative period may precede the postoperative development of significant cardiac morbidity and mortality (including myocardial infarction or unstable angina, congestive cardiac failure, cerebrovascular accidents, and severe arrhythmias). A number of strategies have been examined to reduce these adverse outcomes. The effect of acute β-adrenoceptor blockade in treatment-naive patients is associated with reduction in the haemo-dynamic response to noxious stimuli and decreased ECG evidence of myocardial ischaemia, as well as a reduction in the number of cardiac adverse events. Other drugs (calcium channel antagonists, α2-agonists and adenosine modulators) have a less predictable influence on both myocardial ischaemia and hard cardiac outcomes. There is inadequate evidence at present to define the optimal time course for acute β-blockade, or the groups of patients in whom preoperative β-blockade should be initiated in the absence of contraindications. Nevertheless, addition of β-blockers to the preoperative regimen should be considered in patients with evidence of or at risk for coronary disease undergoing major surgery. There is also evidence that long-term β-adrenoceptor or calcium channel blockade or nitrate therapy for the high-risk cardiac patient offers little protection against silent myocardial ischaemia, nonfatal infarction, cardiac failure and cardiac death.

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]).

Peri-operative troponin I concentration as a marker of long-term postoperative adverse cardiac outcomes - A study in high-risk surgical patients

We have previously demonstrated that the peri‐operative measurement of increased serum concentrations of the cardiac markers troponins I and T and creatine kinase‐MB can be predictors of major cardiovascular outcomes (including cardiac death) at 3 months after surgery. In the present study, we have followed the postoperative course of 157 patients undergoing major vascular surgery or major joint arthroplasty to 1 year using a patient questionnaire, general practitioner follow‐up and case‐notes review. Increased postoperative marker concentrations were defined as values greater than the upper reference limit. Increases in troponin I and troponin T concentrations, as well as a single elevated creatine kinase‐MB and two successively elevated creatine kinase‐MB concentrations were measured in 12, 13, 33 and 15 patients respectively. Thirty‐nine major adverse cardiac outcomes were recorded (cardiac death, myocardial ischaemia, congestive cardiac failure, unstable angina, cerebrovascular accident and major arrhythmias needing active treatment). There was no association between increases in any of these cardiac markers and cardiac death to 1 year. However, increases in troponin I and both a single elevated creatine kinase‐MB and two successively elevated creatine kinase‐MB concentrations were associated with an increased incidence of major cardiac outcomes, including cardiac death, to 1 year (odds ratio [95% confidence intervals] = 4.19 [1.16–14.87], 3.97 [1.65–9.44] and 5.19 [1.60–16.22], respectively).