Incidence Of Perioperative Myocardial Ischemia Research Articles

Dexmedetomidine in modern anesthesiology and intensive care

Background. Sedation is a controlled medical depression of consciousness with the preservation of protective reflexes, independent effective breathing and response to physical stimulation and verbal commands. Sedation is indicated for patients in the intensive care unit in presence of agitation, delirium, withdrawal syndrome of alcohol, drugs or other potent medications and the need to protect the brain (blunt traumatic brain injury, posthypoxic encephalopathy). In addition, at the request of the patient, sedation can be used during invasive diagnostic and treatment procedures.
 Objective. To describe the role of dexmedetomidine in modern anesthesiology and intensive care.
 Materials and methods. Analysis of literature data on this issue.
 Results and discussion. When performing sedation, one should balance between the excessive sedation and its absence. Excessive sedation is accompanied by the lack of contact with the patient, inability to assess the neurological status of the patient, and respiratory depression. If the patient is optimally sedated, he is calm and able to cooperate; he is also adapted to mechanical lung ventilation and other procedures. The target level of sedation according to the Richmond excitation-sedation scale is from 0 to -1. Drugs such as benzodiazepines (diazepam, midazolam, lorazepam), barbiturates (sodium thiopental), propofol, ketamine, inhaled anesthetics (sevoflurane, dexflurane), dexmedetomidine, opioids (morphine, fentanyl, remifentanyl) are used for sedation. Dexmedetomidine is a highly selective α2-adrenoagonist, so it has anxiolytic, sedative, antinociceptive, sympatholytic, and hypothermic actions. In addition, this drug reduces heart rate, suppresses tremor and increases diuresis. The sedative effect of dexmedetomidine is due to the inhibition of neuronal activity in the locus coeruleus of the brain stem. The condition caused by dexmedetomidine is similar to the natural sleep. The use of dexmedetomidine allows to achieve the target level of sedation in a higher percentage of cases than the use of other drugs (propofol, midazolam) (Jacub S.M. et al., 2012). Cooperative sedation is a sedation with the possibility of interaction of the patient with the medical staff. Compared to other drugs, dexmedetomidine increases the patient’s ability to wake up and quickly orient, after which the patient can quickly return to a state of sedation. One of the major complications of critically serious diseases and their treatment is the deterioration of cognitive abilities. Dexmedetomidine has been shown to improve the patient’s cognitive performance by 6.8 points on the John Hopkins scale. In contrast, propofol reduces cognitive function by an average of 12.4 points (Mirski M.A. et al., 2010). Dexmedetomidine has no respiratory depressant effect. Patients on mechanical ventilation do not require discontinuation of dexmedetomidine prior to extubation. Importantly, dexmedetomidine increases coronary blood flow, reduces the incidence of perioperative myocardial ischemia and the risk of perioperative cardiac death. Dexmedetomidine reduces the intensity of pain in the postoperative period and the need for opioids, the incidence of delirium, and the duration of mechanical ventilation. The financial and economic reasonability of dexmedetomidine use has been proved.
 Conclusions. 1. Sedation is indicated for patients in the intensive care unit in presence of agitation, delirium, withdrawal syndrome and the need to protect the brain, as well as during invasive diagnostic and treatment procedures. 2. The target level of sedation is from 0 to -1 on the Richmond excitation-sedation scale. 3. Dexmedetomidine is a highly selective α2-adrenoagonist, which has anxiolytic, sedative, antinociceptive, sympatholytic, and hypothermic action. 4. Dexmedetomidine increases coronary blood flow and reduces the incidence of perioperative myocardial ischemia, the risk of perioperative cardiac death, pain, delirium incidence and the duration of mechanical ventilation.

Pharmacological postconditioning by sevoflurane during cardiac surgery

Optimization of myocardial protection during cardiac surgery with a long period of anoxia infarction using sevoflurane postconditioning of myocardium. to develop the optimal pharmacological postconditioning protocol with sevoflurane for infarction patients ,undergoing cardiac surgery. Two groups were formedfor this study: CON] 00 (n-32) with aortic cross-clamping time 114±15 min and SEV100 group (n-34), where the myocardium anoxia was 119±22 minutes. According to previously developed in the pilot study Protocol, we added sevofturane in the circuit of extracorporeal circulation in a dose of 2.0 vol. % 20 minutes before removing the clamp from the aorta and the first 20 min of reperfusion in the group SE V100. In the group CON1 00 pharnacological postconditioning wasn't conducted. To assess the adequacy of the cardioprotection against ischemic damage in operated patients, we used the following clinical and laboratory parameters: changing the level of troponin T; the concentration of lactate and glucose as a marker of severity of anaerobic metabolism; concentration of proinflammatory cytokines IL-6, IL-8, TNF-alpha in blood serum as reperfusion injury markers. Also we used the registration of central hemodynamics data: measuring the mean invasive blood pressure; central venous pressure; Cardiac output was measured by the method of transesophageal echocardiography TEEcho-CG, calculated left ventricular ejection fraction by Simpson. We evaluated the clinical course of the perioperative period: incidence ofperioperative myocardial ischemia; the need and the duration ofuse of cardiotonic drugs in the perioperative period; the incidence of reperfusion arrhythmias; the frequency of self-recovery heart rate. According to the results of anaerobic metabolism markers, we can conclude that the period of the myocardium anoxia ofpatients in both groups experienced no significant difference. However; a completely different pattern was observed when comparing the proinflammatory cytokines, such as IL-6, IL-8, TNF-a. This confirms that the group SEV] 00 survived the reperfusion is much better than the group CON100. Instrumental examination also showed that the group ofpatients in which pharmacological postconditioning with sevofturane was held signficantly better suffered ischemia and reperfiision injury compared to control group. Self-recovery heart rate after removing the aorta clamp in the group CON100 was observed in 81%, in group SEV100 same - 93%. Similarly, the frequency of myocardial ischemia episodes on the ECG in reperfusion period was two times lower in the group SEV100 compared with group CON100 - 5.8% and 12.5% respectively. Reperfusion arrhythmia is almost 3 times more frequent in the group CON100 - 21,8%, in the group SEV100, where he conducted pharmacological postconditioning with sevoflurane is 8.8%.. Combined with sevoflurane cardioprotection FPC has a much better resistance to myocardial ischemia-reperfusion injury in patients with myocardial infarction time over 100 minutes than monoprotection with cardioplegic solution "Console ". This method can be recommended as an additional method ofprotection against myocardial ischemia-reperfusion injury.

A comparative study of pharmacological myocardial protection between sevoflurane and desflurane at anaesthestic doses in patients undergoing off pump coronary artery bypass grafting surgery.

Background and Aims:Perioperative myocardial ischaemia (PMI) is one of the known complications during off pump coronary artery bypass (OPCAB) surgeries. The length of hospital stay is considerably prolonged in patients with PMI. Myocardial protection is an area which is being widely researched currently to prevent or reduce the incidence of PMI. Over the last decade it has become clear that volatile anaesthetic agents are protective in the setting of PMI and reperfusion. Hence, we planned to study the effect of two different volatile anaesthetics as myocardial protective agents in OPCAB surgery.Methods:A total of 40 patients were enrolled for the study; Group A (sevoflurane, n = 20) and Group B (desflurane, n = 20). All patients had a baseline measurement of Trop-T, creatine phosphokinase-MB (CPKMB) and myocardial performance index (MPI) pre-operatively, which was repeated 4 h after the surgery. Chi-square/Fisher test was used to find the significance of the differences between the two agents.Results:Patients were comparable in demographic, baseline, biochemical and echo criteria. Post-operative CPKMB levels (desflurane - 30.85 ± 2.69 u/L; sevoflurane - 29.05 ± 5.26 u/L, P = 0.7) and number of Trop-T positive patients (Sevoflurane - 9; desflurane - 6, P ≥ 0.05) were comparable. Post-operative MPI indicated decreased left ventricular function in sevoflurane group as compared to desflurane group (P ≤ 0.03).Conclusion:Desflurane exerts better cardioprotective effect than sevoflurane as indicated by better MPI in OPCAB surgeries.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Perioperative myocardial ischemia and isolated systolic hypertension in non-cardiac surgery

To determine whether patients with isolated systolic hypertension (ISH) undergoing non-cardiac surgery have a higher incidence of perioperative myocardial ischemia than normotensive patients and hence a greater risk for perioperative adverse events. After obtaining Research Ethics Board approval, patients were recruited to either an ISH group (systolic blood pressure [SBP]>140mmHg with diastolic blood pressure [DBP]<90mmHg) or a normotensive group (SBP<140mmHg and DBP<90mmHg), according to their resting preoperative blood pressure. The primary outcome was the overall incidence of perioperative myocardial ischemia (PMI) as determined by 48-hr ambulatory Holter monitoring. P values≤0.05 were considered to be statistically significant. A total of 312 (150 ISH and 162 normotensive) patients completed the study. Orthopedic surgery was the most frequent surgical procedure in both groups. The overall incidence of PMI was 19.7% in the ISH group compared with 18.8% in the normotensive group (difference 0.9%; 95% confidence interval [CI], -7.9% to 9.8%). The overall incidence of adverse events was 4.0% in the ISH group compared with 1.9% in the normotensive group (difference 2.2%; 95% CI, -1.6% to 5.9%). In this study, we chose to examine ISH as potential cardiac risk factor for patients undergoing non-cardiac surgery. The incidence of myocardial ischemia, a surrogate outcome, was similar in the two groups. The relatively high incidence of myocardial ischemia (19.2%) was of particular interest in this relatively low cardiac risk surgical population. (ClinicalTrials.gov number, NCT01237652).

Influence of drug eluting stents on surgical revascularisation

Summary Introduction: Drug eluting stents (DES) were introduced in clinical routine to reduce neo- intimal hyperplasia and thus restenosis. Aim of the present study was to analyse the impact of previous PTCA therapy on the clinical outcome of CABG-surgery in a single center experience. Patients and methods: Data of 411 consecutive patients undergoing isolated CABG-surgery within a 10-months period were analysed. 328 patients (79.8%) were previously treated by the in-house interventional cardiology team. Characteristics of patients with and without previous balloon angioplasty (PTCA) and/or stent were compared. Results: 72/328 patients (22%) were treated by percutaneous coronary intervention prior to CABG (14 had PTCA only (19.4%), 36 stents without PTCA (50%) and 22 PTCA and stents (30.6%)). Despite use of DES in 53 patients (91.4%), stent failure was found in 29.2% in the interventional treated collective. Patients treated interventionally were younger (63.0 ± 10.0 years vs 66.1 ± 9.7 y; p 60 IU/l) was more frequent in the PCI-group than in patients who underwent CABG without previous PCI (12.4% vs 6.3%; p <0.01). One year follow-up revealed no differences between the two groups as far as survival and freedom from reintervention were analysed. Conclusions: 80% of the patients who received interventional treatment before CABG-sur- gery presented with a stent. In one third, pa- tients were addressed to surgery, due to stent failure. We observed a higher incidence of perioperative myocardial ischaemia in pa- tients who underwent previous interventional treatment.

Randomized clinical trial of moxonidine in patients undergoing major vascular surgery

Myocardial ischaemia is the leading cause of perioperative morbidity and mortality after surgery in patients with coronary artery disease. The aim of this study was to evaluate the effects of moxonidine, a centrally acting sympatholytic agent, on perioperative myocardial ischaemia and 1-year mortality in patients undergoing major vascular surgery. In this double-blind, placebo-controlled two-centre trial, 141 patients were randomly assigned to receive moxonidine or placebo on the morning before surgery and on the following 4 days. Levels of cardiac troponin I (cTnI) were analysed before surgery and on days 1, 2, 3 and 7 thereafter. Holter electrocardiograms were recorded for 48 h starting before the administration of the study drug. Patients were followed daily during admission and by telephone interview 12 months after surgery. The incidence of raised perioperative cTnI levels or alteration in the ST segment in the Holter electrocardiogram or both was 40 per cent in the moxonidine group and 37 per cent in the placebo group (P = 0.694). All-cause mortality rates within 12 months were 10 per cent in the moxonidine group and 11 per cent in the placebo group (P = 0.870). Small oral doses of moxonidine did not reduce the incidence of perioperative myocardial ischaemia and had no effect on mortality in patients undergoing vascular surgery. NCT00244504 (http://www.clinicaltrials.gov).

Carotid artery stenting versus endarterectomy in relation to perioperative myocardial ischemia, troponin T release and major cardiac events

Carotid artery stenting (CAS) is less invasive than endarterectomy. This study examined differences in perioperative myocardial ischemia, troponin T release and clinical cardiac events in patients undergoing CAS compared with endarterectomy. In an observational study, CAS was performed in 24 and carotid endarterectomy in 44 patients. Before surgery, clinical risk factors were noted and dobutamine stress echocardiography was performed for cardiac risk assessment. Perioperative continuous 72-h 12-lead electrocardiographic monitoring was used for myocardial ischemia detection. Troponin T (>0.03 ng/ml) was measured on postoperative days 1, 3, 7 or before discharge. Cardiac events (cardiac death or Q-wave myocardial infarction) were noted during hospital stay and during follow-up (mean: 1.2 years). No significant differences were observed between patients with CAS and endarterectomy in terms of baseline clinical characteristics, dobutamine stress echocardiography results and cardiovascular medication. Perioperative myocardial ischemia was detected in nine patients (13%), perioperative troponin T release in seven patients (10%), early cardiac events in one patient (1%) and late cardiac events in three patients (4%). Significantly less perioperative myocardial ischemia was observed in patients with CAS compared with endarterectomy (0 versus 21%, P=0.02). Troponin T release was also significantly lower in CAS, compared with endarterectomy (0 versus 16%, P=0.04). Early (0 versus 2%, P=0.5) and late (0 versus 7%, P=0.2) cardiac events were lower after CAS, compared with endarterectomy, although these differences were not significant. CAS is associated with a lower incidence of perioperative myocardial ischemia and troponin T release, compared with endarterectomy.

Acute peri‐operative beta blockade in intermediate‐risk patients

Peri-operative beta-blockade has been shown to reduce the incidence of postoperative cardio- vascular complications including cardiac death in high-risk non-cardiac surgical patients. However, the recent analysis by Lindenauer et al. suggests that it is inappropriate to administer beta-blockers blindly to all surgical patients. In an attempt to determine the appropriateness of peri-operative beta-blocker administration across patients with a spectrum of cardiovascular risks, we have examined studies of intermediate-risk patient groups (that is those undergoing intermediate risk surgery or those with a Lee Revised Cardiac Risk Score of < or =2). We analysed data from randomised prospective studies of the effects of acute peri-operative beta-blockade on the incidence of peri-operative myocardial ischaemia. By examining the demographics and surgical interventions in these patients, we have compared these studies with other studies of peri-operative silent myocardial ischaemia representing patients of similar risk. We thus estimated the expected long-term postoperative cardiovascular complication rate associated with myocardial ischaemia in these patients in terms of number needed to treat for ischaemia prevention and for prevention of major cardiovascular complications. Prevention of peri-operative myocardial ischaemia with acute beta-blockade in non-cardiac surgical patients with 1-2 RCRI clinical risk factors can be achieved with a number needed to treat of 10. It is not associated with a significant increase in drug associated side-effects. However, acute beta-blockade shows no real benefit in the prevention of major cardiovascular complications in intermediate risk non-vascular surgical patients with a number-needed-to-treat of 833. Vascular surgical patients undergoing intermediate-risk surgery may benefit from the protective effects of acute peri-operative beta-blockade, however, with a number-needed-to-treat of 68 it would require a randomised clinical trial of over 24,000 patients to prove their efficacy.

Effect of Clonidine on Cardiovascular Morbidity and Mortality after Noncardiac Surgery

The authors conducted a study to determine if prophylactic clonidine reduces the incidence of perioperative myocardial ischemia and postoperative death in noncardiac surgery patients. Patients were administered clonidine or placebo (orally and a patch) the night before surgery and the morning of surgery. The patch (clonidine or placebo) was removed after 4 days. Clonidine reduced the rate of postoperative death up to 2 years; perioperative myocardial ischemia was significantly reduced; and prophylactic clonidine had minimal hemodynamlc effects.

Postoperative 12‐lead ECG predicts peri‐operative myocardial ischaemia associated with myocardial cell damage

Peri-operative myocardial ischaemia is the single most important risk factor for an adverse cardiac outcome after non-cardiac surgery. The present study examines whether intermittent 12-lead ECG recordings can be used as an early warning tool to identify patients suffering from peri-operative myocardial ischaemia and subsequent myocardial cell damage. Fifty-five vascular surgery patients at risk for or with a history of coronary artery disease were monitored for peri-operative myocardial ischaemia using intermittent 12-lead ECG recordings taken pre-operatively and at 15 min, 20 h, 48 h, 72 h and 84 h postoperatively. The effectiveness of the 12-lead ECG was gauged by examining concordance with continuous 3-channel Holter monitoring and capturing peri-operative myocardial ischaemia by serial analyses of creatine kinase myocardial band isoenzyme and cardiac troponin T and I. The incidence of peri-operative myocardial ischaemia detected by 12-lead ECG was 44% and was identifiable in most patients (88%) 15 min after surgery. The incidence of peri-operative myocardial ischaemia detected by continuous monitoring was 53%, with the most severe episodes occurring intra-operatively and during emergence from anaesthesia. The concordance of the 12-lead method with continuous monitoring was 72%. The concordance of creatine kinase myocardial band isoenzyme activity with the 12-lead method was 71% and with Holter monitoring 57%. The concordance of mass concentration of creatine kinase myocardial band with 12-lead ECG recordings was 75%, and the corresponding value for Holter monitoring was 68%. The concordance of cardiac troponin T and I levels with the 12-lead method was 85% and 87%, respectively, and concordance with Holter monitoring was 72% and 66%, respectively. The postoperative 12-lead ECG identified peri-operative myocardial ischaemia associated with subsequent myocardial cell damage in most patients undergoing vascular surgery.

Risk factors for perioperative myocardial ischemia in carotid artery endarterectomy

Objective: To identify variables associated with perioperative myocardial ischemia in patients undergoing carotid artery endarterectomy (CEA). Design: Prospective, observational study. Setting: University-affiliated hospital operating room and intensive care unit. Participants: One hundred twenty-eight consecutive patients who underwent CEA during a 7-year period. Interventions: Patients had general anesthesia with sevoflurane or isoflurane. CEA was performed by standard methods with shunting if clinically indicated. Holter electrocardiogram (ECG) monitoring was performed during surgery and 24 hours after surgery. Measurements and main results: The incidence of perioperative myocardial ischemia was examined, and perioperative risk factors were analyzed. Nineteen patients (15%) showed significant perioperative ECG abnormalities indicative of myocardial ischemia (10 patients during surgery, 12 patients after surgery, and 3 patients both during and after surgery). Multivariate analysis showed perioperative myocardial ischemia to be significantly associated with a history of angina (odds ratio, 11.68; 95% confidence interval, 2.64–51.70) and a history of hypertension (odds ratio, 14.08; 95% confidence interval, 1.51–131.04). Conclusion: The data indicate that perioperative myocardial ischemia defined as an ECG abnormality does not often occur in patients undergoing CEA. However, angina and hypertension may be important risk factors warranting further investigation.

Perioperative Management of the Patient with Cardiovascular Disease Undergoing Non-cardiac Surgery

The risk of developing cardiovascular complications during and after surgery depends on the nature of the surgery undertaken, and increases with the age of the patient. As many as 10% of all patients undergoing non-cardiac surgery have, or are at risk of having, cardiovascular disease (CVD, Figure 1). As many as 30% of patients over 65 years of age and 60% of patients undergoing vascular surgery will have significant CVD. Within this latter group, surgical procedures requiring aortic crossclamping are associated with a particularly high incidence of perioperative myocardial ischaemia.

Prevention of perioperative myocardial ischemia--an update

Perioperative cardiac morbidity and mortality are a major health care challenge with important individual as well as economic aspects. Up to 30% of all perioperative complications and up to 50% of all postoperative deaths are related to cardiac causes. Perioperative myocardial ischemia, which occurs in more than 40% of patients with or at risk for coronary artery disease and undergoing noncardiac surgery, represents a dynamic predictor of postoperative cardiac complications. Long-duration myocardial ischemia and ischemic episodes associated with myocardial cell damage are particularly of prognostic relevance. In patients suffering from this type of ischemia, the incidence of adverse cardiac outcome is increased up to 20-fold. Reducing the incidence of perioperative myocardial ischemia is associated with a decrease in adverse cardiac outcome. Important issues related to perioperative myocardial ischemia are hematocrit level, body temperature, and hemodynamic variables. In contrast, the choice of anesthetic agents and techniques appears to be less important. Perioperative administration of anti-ischemic drugs in patients at risk, however, leads to a further decrease in the incidence of myocardial ischemia and to an improvement in patient outcome. Recent studies suggest that alpha 2-agonists and particularly beta-adrenoreceptor blocking agents are effective anti-ischemic drugs in the perioperative setting. Perioperative administration of beta-adrenoreceptor blocking agents in coronary risk patients undergoing noncardiac surgery is associated with a reduced rate of postoperative cardiac complications and an improvement in long-term outcome. This is particularly relevant in high risk patients with preoperative stress-induced ischemic episodes. In clinical practice, therefore, chronically administered anti-ischemic drugs should also be administered on the day of surgery and during the postoperative period. In untreated patients with or at risk for coronary artery disease and who have to undergo urgent surgical procedures without the opportunity of preoperative anti-ischemic intervention, perioperative administration of beta-adrenoreceptor blocking agents is mandatory.

Myocardial ischemia correlates with reduced fibrinolytic activity following peripheral vascular surgery

Study Objectives: To evaluate the relationship between perioperative ischemia and serial concentrations of D-dimer, which is a sensitive and specific marker of fibrinolytic activity. Myocardial ischemia and infarction are well-recognized complications of peripheral vascular surgery. We hypothesized that patients at increased risk of perioperative myocardial ischemia might be identified preoperatively by abnormal hemostatic indices. Design: Prospective clinical outcomes study. Setting: A 1,124-bed tertiary care medical center. Patients: 42 ASA physical status II, III, and IV patients undergoing peripheral vascular surgery. Interventions: Serial D-dimer concentrations were measured preoperatively, and at 24 and 72 hours postoperatively. Continuous 12-lead ST-segment monitoring (Mortara Instrument, Inc., Milwaukee, WI) was performed with the acquisition of a 12-lead ECG every 20 seconds for 72 hours. Measurements and Main Results: D-dimer measurements were performed in duplicate using the Dimer Gold assay (American Diagnostica, Greenwich CT). Ischemic episodes, as defined by continuous 12-lead ST-segment monitoring, occurred in 49% of patients. There were no demographic differences between ischemic and nonischemic groups. Although baseline D-dimer concentrations were not statistically significantly different between groups, patients experiencing perioperative myocardial ischemia generated significantly less D-dimer during the perioperative period ( p = 0.014). Conclusions: Patients with an impaired fibrinolytic response, as defined by reduced generation of D-dimer, experienced an increased incidence of perioperative myocardial ischemia.

Diabetes and Not Lack of Treatment with Atenolol Predicts Decreased Survival after Noncardiac Surgery

Veterans Administration Medical Center; Anesthesia (129); San Francisco, California 94121;awallace@best.comIn Reply:-Thank you for allowing me to respond to Dr. Leung's comments about the two studies. [1,2]In February 1998, Dr. Leung wrote to Anesthesiology with six criticisms of Anesthesiology and New England Journal of Medicine articles. These criticisms included suggestions that it was inappropriate to withhold study drug from patients who might have a side effect, questions concerning the statistics in the New England Journal of Medicine article, requests for more postoperative hemodynamic data, questions about the withholding of beta blockade, interactions of diabetes and atenolol, and the lack of women in the study. I responded to all of these criticisms in writing, and those comments were published in Anesthesiology. [3]Dr. Leung was dissatisfied with the results of the letter to Anesthesiology and has sent a second letter to Anesthesiology with more criticisms, including:1. “Their study did not provide statistical support for such a claim.”2. “… this indicated that the effect of atenolol was not different from that of placebo, i.e., no influence of atenolol on survival.3. “[Greek small letter beta]-adrenergic blocking agents have reduced incidence of morbidity and mortality can not be supported by the current studies.”4. “… the recent popularized use of perioperative beta blockade is based on misinformation.”5. “Physicians caring for such patients should reevaluate the validity of recommending perioperative beta blockade for improved survival.”We strongly disagree with Dr. Leung and her misunderstanding of the results of the two manuscripts. [1,2]The primary end-point of the atenolol [2]study was the reduction of perioperative myocardial ischemia by atenolol. Perioperative administration of atenolol for 1 week to patients at high risk for coronary artery disease significantly reduced the incidence of postoperative myocardial ischemia (P = 0.029). Furthermore, a secondary finding was that reductions in perioperative myocardial ischemia were associate with reductions in the risk for death at 2 yr (P = 0.025). The primary end-point of the atenolol long-term study [4]was the effect of atenolol on 2-yr mortality. In patients who have or are at risk for coronary artery disease who must undergo noncardiac surgery, treatment with atenolol during hospitalization reduced mortality (P = 0.019) and the incidence of cardiovascular complications for as long as 2 yr after surgery (P = 0.008). These two studies provide clear and statistically significant evidence to support the claims that perioperative atenolol reduced incidence of morbidity and mortality and improves survival in patients at risk for cardiac morbidity.Dr. Leung does not understand the interpretation of univariable and multivariable models presented in Table 2of the Mangano et al. manuscript. [4]Once statistical significance is established, it is acceptable to do a secondary analysis of the data to look for other predictors of outcomes. We demonstrated clearly that atenolol reduced the risk of death. Diabetes mellitus and ischemia increased the risk of death. In the multivariable model we demonstrated that diabetes was statistically significant, but once patients with diabetes were excluded there was not sufficient power to demonstrate the effect of atenolol. Thirty-one percent of the patients in this trial had diabetes. If one exclude 31% of the patients in a trial, power is lost. That in no way brings the results into question; it simply implies that if one excludes 31% of the patients, one also loses power to see the effect. Furthermore, Dr. Leung is incorrect in stating that P = 0.06 (6% type I error) is not significantly when P = 0.05 (5% type I error) is suddenly significant. It is simply the difference between a 5% and 6% chance of a type I error. Perioperative administration of atenolol reduces the incidence of perioperative myocardial ischemia, postoperative mortality, and cardiovascular complications.Dr. Leung's statement that the use of perioperative beta blockade is based on misinformation is incorrect. It is important to understand statistics and study design before making such a statement. Physicians should clearly evaluate any therapy. Many trials of beta-blocker use demonstrate benefits in nonsurgical patients, including the ISIS-1 (International Study of Infact Survival), [5]the MIAMI (Metoprolol in Acute Myocardial Infarction), [6]the MAPHY (Metoprolol versus Thiazide Diuretics in Hypertension), [7]and the ASIST (Atenolol Silent Ischemia Study)[8]trials. We added to this abundant literature and have clearly demonstrated that perioperative beta blockade improves survival in surgical patients at risk for cardiac morbidity.Arthur Wallace, M.D., Ph.D.Veterans Administration Medical Center; Anesthesia (129); San Francisco, California 94121;awallace@best.com(Accepted for publication November 11, 1998.)

Beta Blockade in Non-cardiac Surgical Patients

Beta Blockade in Non-cardiac Surgical Patients

ST segment changes following retinal surgery

Study Objective: To describe the perioperative cardiac morbidity in adult patients undergoing retinal surgery using continuous Holter monitoring. Design: Prospective study. Setting: University hospital. Patients: 56 patients scheduled for elective retinal surgery with local anesthesia. Interventions: Patients were monitored continuously for 24 hours using a Holter recorder. Blood samples for creatine phosphokinase (CPK) and serum myocardial creatine phosphokinase (CPK-MB) were taken preoperatively and 24 hours postoperatively. The characteristics of myocardial ischemia were compared according to the number of risk factors for ischemic heart disease. Measurements and Main Results: The overall incidence of perioperative myocardial ischemia was high: 26.7% (n = 15). These patients exhibited 41 episodes of ischemia with mean ST segment change from baseline of 2.2 ± 0.7 mm. However, almost all (93.3%) ischemic episodes were silent. Patients with two risk factors or more had 77% more episodes of ischemia than patients with one risk factor (p < 0.005), and the duration of ischemia was 47 ± 22.5 minutes compared with 34.8 ± 27.5 minutes (p = NS). The first episode of ischemia occurred an average of 10 hours after surgery. No patient had intraoperative evidence of ischemia. Half of the ischemic episodes were associated with an increase in heart rate. No patient had evidence of acute myocardial infarction. Conclusion: Retinal surgery with local anesthesia is accompanied by a high incidence of postoperative myocardial ischemia. No negative outcome was correlated to the occurrence of postoperative myocardial ischemia. The significance of these findings has yet to be evaluated.

Anesthetic management and perioperative surveillance

The intraoperative management of the high-risk patient has received a great deal of attention and research during the past decade. Based on the available evidence, there appears to be no one best anesthetic technique or agent. More importantly, the goals of intraoperative management are to avoid myocardial ischemia, which include preventing tachycardia, and maintaining normothermia and adequate hematocrit. Perioperative monitoring includes transesophageal echocardiography, pulmonary artery catheter and ST segment monitoring. Perioperative pharmacological treatment with alpha-2 agonists and beta-adrenergic blocking agents are associated with a reduced incidence of perioperative myocardial ischemia and improved long-term survival, respectively. Future research will be required to determine whether prophylactic therapy or early treatment of perioperative myocardial ischemia will lead to improved outcome.

Cardiopulmonary bypass and the inflammatory response: A role for serine protease inhibitors?

Cardiopulmonary bypass has been shown to activate various inflammatory cascades in the body, resulting in pathophysiological changes that may affect patient outcome after cardiac surgery. Many of these inflammatory cascades are enzyme mediated, involving serine proteases. This report reviews the mechanisms of bypass-mediated activation of the inflammatory cascades and outlines the role of serine protease inhibitors in ameliorating the consequences of the inflammatory response. Experimental data are reviewed on the action of aprotinin in inhibiting the intrinsic coagulation system and in limiting the contact activation of blood platelets and leukocytes. Also reviewed is the role of aprotinin in impacting the incidence of perioperative myocardial ischemia and the central nervous system dysfunction and stroke that are not infrequent complications of surgery with cardiopulmonary bypass.