Balachundhar Subramaniam

Ketamine as Adjuvant Analgesic to Opioids: A Quantitative and Qualitative Systematic Review

Animal studies on ketamine and opioid tolerance have shown promising results. Clinical trials have been contradictory. We performed a systematic review of randomized, double-blind clinical trials of ketamine added to opioid analgesia. Thirty-seven trials with 51 treatment arms and 2385 patients were included. Studies were divided into 5 subgroups: IV ketamine as single dose (n = 11), continuous infusion (n = 11), patient-controlled analgesia (PCA) (n = 6), epidural ketamine with opioids (n = 8), and studies in children (n = 4). Outcome measures included pain scores, time to first request for analgesia, supplemental analgesics, and adverse events. Efficacy was estimated by statistical significance (P <0.05) of outcome measures as reported in studies and also by calculation of weighted mean difference for pain scores during the first 24 h after surgery. As compared to morphine alone, IV PCA with ketamine and morphine did not improve analgesia. Intravenous infusion of ketamine decreased IV and epidural opioid requirements in 6 of 11 studies. A single bolus dose of ketamine decreased opioid requirements in 7 of 11 studies. Five of 8 trials with epidural ketamine showed beneficial effects. Adverse effects were not increased with small dose ketamine. We conclude that small dose ketamine is a safe and useful adjuvant to standard practice opioid-analgesia.

Continuous perioperative insulin infusion decreases major cardiovascular events in patients undergoing vascular surgery: a prospective, randomized trial.

Background:A growing body of evidence suggests that hyperglycemia is an independent predictor of increased cardiovascular risk. Aggressive glycemic control in the intensive care decreases mortality. The benefit of glycemic control in noncardiac surgery is unknown. Methods:In a single-center, prospective, unblinded, active-control study, 236 patients were randomly assigned to continuous insulin infusion (target glucose 100–150 mg/dl) or to a standard intermittent insulin bolus (treat glucose > 150 mg/dl) in patients undergoing peripheral vascular bypass, abdominal aortic aneurysm repair, or below- or above-knee amputation. The treatments began at the start of surgery and continued for 48 h. The primary endpoint was a composite of all-cause death, myocardial infarction, and acute congestive heart failure. The secondary endpoints were blood glucose concentrations, rates of hypoglycemia (< 60 mg/dl) and hyperglycemia (> 150 mg/dl), graft failure or reintervention, wound infection, acute renal insufficiency, and duration of stay. Results:The groups were well balanced for baseline characteristics, except for older age in the intervention group. There was a significant reduction in primary endpoint (3.5%) in the intervention group compared with the control group (12.3%) (relative risk, 0.29; 95% confidence interval, 0.10–0.83; P = 0.013). The secondary endpoints were similar. Hypoglycemia occurred in 8.8% of the intervention group compared with 4.1% of the control group (P = 0.14). Multivariate analysis demonstrated that continuous insulin infusion was a negative independent predictor (odds ratio, 0.28; 95% confidence interval, 0.09–0.87; P = 0.027), whereas previous coronary artery disease was a positive predictor of adverse events. Conclusion:Continuous insulin infusion reduces perioperative myocardial infarction after vascular surgery.

Perioperative and long-term morbidity and mortality after above-knee and below-knee amputations in diabetics and nondiabetics.

We performed a retrospective review of a vascular surgery quality assurance database to evaluate the perioperative and long-term morbidity and mortality of above-knee amputations (AKA, n = 234) and below-knee amputations (BKA, n = 720) and to examine the effect of diabetes mellitus (DM) (181 of AKA and 606 of BKA patients). All patients in the database who had AKA or BKA from 1990 to May 2001 were included in the study. Perioperative 30-day cardiac morbidity and mortality and 3-yr and 10-yr mortality after AKA or BKA were assessed. The effect of DM on 30-day cardiac outcome was assessed by multivariate logistic regression and the effect on long-term survival was assessed by Cox regression analysis. The perioperative cardiac event rate (cardiac death or nonfatal myocardial infarction) was at least 6.8% after AKA and at most 3.6% after BKA. Median survival was significantly less after AKA (20 mo) than BKA (52 mo) (P < 0.001). DM was not a significant predictor of perioperative 30-day mortality (odds ratio, 0.76 [0.39–1.49]; P = 0.43) or 3-yr survival (Hazard ratio, 1.03 [0.86–1.24]; P = 0.72) but predicted 10-yr mortality (Hazard ratio, 1.34 [1.04–1.73]; P = 0.026). Significant predictors of the 30-day perioperative mortality were the site of amputation (odds ratio, 4.35 [2.56–7.14]; P < 0.001) and history of renal insufficiency (odds ratio, 2.15 [1.13–4.08]; P = 0.019). AKA should be triaged as a high-risk surgery while BKA is an intermediate-risk surgery. Long-term survival after AKA or BKA is poor, regardless of the presence of DM.

Perioperative diastolic dysfunction during vascular surgery and its association with postoperative outcome

OBJECTIVE To assess the association of perioperative cardiac dysfunction during elective vascular surgery with postoperative outcome. BACKGROUND Patients with normal systolic function can have isolated diastolic dysfunction. Routine preoperative evaluation of left ventricular (LV) function does not include an assessment of diastolic function for risk stratification. We hypothesized that perioperative assessment of both diastolic and systolic function with transesophageal echo (TEE) may improve our ability to predict postoperative outcome. METHODS Perioperative TEE examinations were carried out on patients undergoing elective vascular surgery under general anesthesia. Abnormal systolic function was defined as LV ejection fraction (LVEF) <40%. Left ventricular diastolic function was assessed using transmitral flow propagation velocity (Vp); Vp <45 cm/sec was considered abnormal. We determined the association between LV function and the primary outcome of postoperative adverse outcome, defined as one or more adverse events: myocardial infarction (MI), congestive heart failure (CHF), significant arrhythmia, prolonged intubation, renal failure, and death. RESULTS Three hundred thirteen patients undergoing vascular surgery were studied. We found that 8% (n = 24) of patients had isolated systolic dysfunction, 43% (n = 134) had isolated diastolic dysfunction, and 24% (n = 75) both systolic and diastolic dysfunction. The most common postoperative adverse outcome was CHF 20% (n = 62). By multivariate logistic regression, we found that patient age, Vp, type of surgery, female gender, and renal failure were predictive of postoperative adverse outcome. CONCLUSION The presence of perioperative diastolic dysfunction as assessed with Vp is an independent predictor of postoperative CHF and prolonged length of stay after major vascular surgery. Patient age, gender, type of surgery, and renal failure were also predictors of outcome. Perioperative systolic function was not a predictor of postoperative outcome in our patients.

Three-Dimensional Echocardiographic Assessment of Changes in Mitral Valve Geometry After Valve Repair

BACKGROUND Application of annuloplasty rings during mitral valve (MV) repair has been shown to significantly change the mitral annular geometry. Until recently, a comprehensive two-dimensional echocardiographic evaluation of annular geometric changes was difficult owing to its nonplanar orientation. In this study, an analysis of the three-dimensional intraoperative transesophageal echocardiographic evaluation of the MV annulus is presented before and immediately after repair. METHODS We performed three-dimensional geometric analysis on 75 patients undergoing MV repair during coronary artery bypass graft surgery for mitral regurgitation or myxomatous mitral valve disease. Geometric analysis of the MV was performed before and immediately after valve repair with full rings and annuloplasty bands. The acquired three-dimensional volumetric data were analyzed in the operating room. Specific measurements included annular diameter, leaflet lengths, the nonplanarity angle, and the circularity index. Before and after repair data were compared. RESULTS Complete echocardiographic assessment of the MV was feasible in 69 of 75 patients (92%) within 2 to 3 minutes of acquisition. Placement of full rings resulted in an increase in the nonplanarity angle or a less saddle shape of the native mitral annulus (137 +/- 14 versus 146 +/- 14; p = 0.002. By contrast, the nonplanarity angle did not change significantly after placement of partial rings. CONCLUSIONS Mitral annular nonplanarity can be assessed in the operating room. Application of full annuloplasty rings resulted in the mitral annulus becoming more planar. Partial annuloplasty bands did not significantly change the nonplanarity angle. Neither of the two types of rings restored the native annular planarity.

Effect of prophylactic ondansetron on postoperative nausea and vomiting after elective craniotomy.

This prospective, randomized, placebo-controlled, double-blind study was designed to evaluate the efficacy of ondansetron, a 5-HT3 antagonist, in preventing postoperative nausea and vomiting (PONV) after elective craniotomy in adult patients. The authors also tried to discover certain predictors for postcraniotomy nausea and vomiting. We studied 170 ASA physical status I and II patients, aged 15 to 70 years, undergoing elective craniotomy for resecting various intracranial tumors and vascular lesions. A standardized anesthesia technique and postoperative analgesia were used for all patients. Patients were divided into two groups and received either saline placebo (Group 1) or ondansetron 4 mg (Group 2) intravenously at the time of dural closure. Patients were extubated at the end of surgery and episodes of nausea and vomiting were noted for 24 hours postoperatively in the neurosurgical intensive care unit. Demographic data, duration of surgery, and anesthesia and analgesic requirements were comparable in both groups. Overall, a 24-hour incidence of postoperative emesis was significantly reduced in patients who received ondansetron compared with those who received a saline placebo (39% in Group 1 and 11% in Group 2, P = .001). There was a significant reduction in the frequency of emetic episodes and rescue antiemetic requirement in patients treated with ondansetron; however, ondansetron did not significantly reduce the incidence of nausea alone (14% in Group 2 vs 5% in Group 1, P = .065). Prophylactic ondansetron had a favorable influence on PONV outcome measures such as patient satisfaction and number needed to prevent emesis (3.5). Side effects were similar in both groups. We conclude that ondansetron 4 mg given at the time of dural closure is safe and effective in preventing emetic episodes after elective craniotomy in adult patients.

Preoperative Epidural Ketamine in Combination with Morphine Does Not Have a Clinically Relevant Intra- and Postoperative Opioid-Sparing Effect

In this prospective, randomized, and double-blinded clinical trial, we evaluated the efficacy of preincisional administration of epidural ketamine with morphine compared with epidural morphine alone for postoperative pain relief after major upper-abdominal surgery. We studied 50 ASA I and II patients undergoing major upper-abdominal procedures. These patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 &mgr;g/kg, whereas those in Group 2 received epidural ketamine 1 mg/kg combined with 50 &mgr;g/kg of morphine 30 min before incision. Intraoperative analgesia was provided in addition, with IV morphine, and the requirement was noted. A blinded observer using a visual analog scale for pain assessment observed patients for 48 h after surgery. Additional doses of epidural morphine were provided when the visual analog scale score was more than 4. Analgesic requirements and side effects were compared between the two groups. There were no differences between the two groups with respect to age, sex, weight, or duration or type of the surgical procedures. The intraoperative morphine requirement was significantly (P = 0.018) less in Group 2 patients (median, 6.8 mg; range, 3–15 mg) compared with patients in Group 1 (median, 8.3 mg; range, 4.5–15 mg). The time for the first requirement of analgesia was significantly (P = 0.021) longer (median, 17 h; range, 10–48 h) in Group 2 patients than in Group 1 (median, 12 h; range, 4–36 h). The total number of supplemental doses of epidural morphine required in the first 48 h after surgery was comparable (P = 0.1977) in both groups. Sedation scores were similar in both groups. One patient in Group 2 developed hallucinations after study drug administration. None of the patients in either group developed respiratory depression. Other side effects, such as pruritus, nausea, and vomiting, were also similar in both groups. Although the addition of ketamine had synergistic analgesic effects with morphine (reduced intraoperative morphine consumption and prolonged time for first requirement of analgesia), there was no long- lasting preemptive benefit seen with this combination (in terms of reduction in supplemental analgesia) for patients undergoing major upper-abdominal procedures.

Evaluation of the safety and efficacy of epidural ketamine combined with morphine for postoperative analgesia after major upper abdominal surgery

STUDY OBJECTIVE To evaluate the efficacy of the combination of epidural ketamine and morphine compared with epidural morphine alone for postoperative pain relief following major upper abdominal surgery. STUDY DESIGN Prospective, randomized, double-blinded study. SETTING Tertiary care referral and teaching hospital. PATIENTS 46 ASA physical status I and II patients who underwent major upper abdominal procedures. INTERVENTIONS Patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg whereas patients in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine postoperatively. MEASUREMENTS A blinded observer using a visual analog scale (VAS) for pain assessment followed up patients for 48 hours postoperatively. Top-up dose of epidural morphine was provided when VAS was higher than 4. Analgesic requirements and side effects were compared between the two groups. RESULTS Only 40 patients completed the study. There were no differences between the two groups with respect to age, gender, weight, duration, or type of surgical procedure or intraoperative opioid requirements. Onset of analgesia was faster (p < 0.001) in Group 2 (11 min) than in Group 1 patients (25 min). The time for first requirement of analgesia was significantly (p < 0.01) longer (19.8 +/- 9.8 hours) in Group 2 patients than Group 1 (12.8 +/- 6.2 hours). Total number of supplemental doses of epidural morphine required in the first 48 hours postoperatively was also significantly less (p < 0.005) in Group 2 compared to Group 1. Patients in Group 2 had higher sedation scores than Group I patients for the first 2 hours postoperatively. None of the patients in either group developed hallucinations or respiratory depression. Other side effects such as pruritus, nausea, and vomiting were also similar in both groups. CONCLUSIONS The addition of epidural ketamine 1 mg/kg to morphine 50 microg/kg improved analgesia after major upper abdominal surgery without increasing side effects.

Echocardiography for management of hypotension in the intensive care unit.

Hypotension is a common problem in critically ill patients. Rapid diagnosis and intervention may prevent this deterioration and improve eventual outcome. Echocardiography may make a critical difference in the rapid diagnosis of both common and uncommon but important causes of hypotension, such as pericardial tamponade. The differential diagnosis for hypotension differs between acutely admitted septic or trauma patients and the chronic patient in the intensive care unit. A better approach to patient evaluation is the performance of a comprehensive evaluation on every patient. A comprehensive examination is less likely to miss an unexpected diagnosis. With practice, a complete examination may be performed in minutes. Preload, contractility, systolic function (global and focal), and assessment of diastolic dysfunction (common cause of congestive heart failure) can be performed quickly. Specific situations like pericardial tamponade, pulmonary embolism, left ventricular outflow tract obstruction, unexplained hypoxemia, and aortic dissection, among others, can all be reliably performed using transesophageal echocardiography. Appropriate training and utilization of this technology will essentially help better manage hypotension in critically ill patients and thereby may improve their outcome. An algorithm to this effect has been suggested, although the same results can be achieved with different algorithms or approaches.

Increased glycemic variability in patients with elevated preoperative HbA1C predicts adverse outcomes following coronary artery bypass grafting surgery.

BACKGROUND:In the setting of protocolized glycemic control, the relationship between postoperative glycemic variability on major adverse events (MAEs) after cardiac surgery is unknown for patients with increased preoperative hemoglobin A1C (HbA1C >6.5%). In this study, we sought to establish (a) whether postoperative glycemic variability is associated with MAEs after CABG surgery and (b) whether preoperative HbA1C could identify patients at increased risk of postoperative glycemic variability. METHODS:Patients undergoing coronary artery bypass grafting with or without valvular surgery from January 2008 to May 2011 were enrolled in this prospective, single-center, observational cohort study. Demographic, intraoperative, and postoperative outcome data were obtained from institutional data collected for the Society of Thoracic Surgery (STS) database. The primary outcome, MAE was a composite of in-hospital death, myocardial infarction (MI), reoperations, sternal infection, cardiac tamponade, pneumonia, stroke, or renal failure. Glycemic variability in the postoperative period was assessed by the coefficient of variation (CV). CV was used as quartiles for the multivariate logistic regression. Variable selection in multivariable modeling was based on clinical and statistical significance and was performed in a hierarchical fashion. RESULTS:Of the 1461 patients enrolled, 9.8% had an MAE. Based on the established target of HbA1C <6.5% for the diagnosis of diabetes mellitus, we considered HbA1C as a binary variable (<6.5% and ≥6.5%) in our primary analysis. Multivariate logistic regression analyses for the preoperative variables only revealed that preoperative HbA1C (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1–2.3; P = 0.02), history of MI (OR, 1.9; 95% CI, 1.3–2.8; P = 0.001), and STS risk score per quartile (OR, 1.7; 95% CI, 1.4–2.1; P < 0.001) were associated with MAEs. When postoperative variables were included in the analyses, postoperative glycemic variability (CV per quartile) in the intensive care unit (OR, 1.3; 95% CI, 1.1–1.5; P = 0.03), mean glucose levels averaged over the first 4 postoperative hours (OR, 1.2; 95% CI, 1.0–1.4; P = 0.03), history of MI (OR, 1.8; 95% CI, 1.2–2.6; P = 0.004), and STS risk score per quartile (OR, 1.6; 95% CI, 1.3–2.0; P < 0.001) were associated with MAEs. Glycemic variability as assessed by CV was increased postoperatively in patients with preoperative HbA1C ≥6.5% (0.20 ± 0.09 vs 0.16 ± 0.07, P < 0.001). CONCLUSIONS:Postoperative glycemic variability is associated with MAEs after cardiac surgery. Glycemic variability is only measured when the patient leaves the intensive care unit, and there is no opportunity to intervene earlier. Preoperative HbA1C identifies risk for postoperative glycemic variability and may provide a more rational guide for targeting measures to reduce variability.