Patient Controlled Analgesia Used to Assess the Efficacy and Potency of a New Opioid

Patient controlled analgesia (PCA) is widely used for the management of postoperative pain. PCA also permits a comparison to be made among analgesics in the clinical setting because it limits the variability introduced by third parties. Use of PCA to establish efficacy and potency data for an investigational drug, pentamorphone, compared with morphine is reported. Pentamorphone was found to be more efficacious than morphine in the first hour after surgery because significantly more patients were able to achieve a visual analogue scale of less than 30 mm with pentamorphone. Thereafter pentamorphone and morphine were found to be equally efficacious. Initially pentamorphone may be more potent than morphine based on the greater volume of morphine used in the first hour of therapy. However, a potency ratio could not be determined because this result was under conditions of unequal analgesia. The potency ratio determined at 24 h of therapy under equianalgesic conditions (252:1) is similar to previously reported potency data from laboratory studies (200:1). This study supports the use of PCA as a model to investigate and compare new drugs to establish their efficacy and potency

A comparison of amrinone with sodium nitroprusside for control of hemodynamics during infrarenal abdominal aortic surgery

The control of hemodynamic changes during surgical resection of abdominal aortic aneurysms (AAA) remains a challenge to anesthesiologists. In the past, hypertensive episodes have been treated with sodium nitroprusside (SNP). However, amrinone may provide some benefits when compared with SNP because of its positive inotropic and vasodilatory properties. Therefore, the purpose of this study was to compare amrinone with SNP for hemodynamic control during AAA surgery. This study was a prospective, randomized investigation. This study was performed at a single university hospital. This study included 20 patients undergoing AAA resection. After institutional review board approval, participants were randomized to receive either SNP (group N = 10) or amrinone (group A = 10). Both agents were started 10 minutes before aortic cross-clamping and discontinued 10 minutes before unclamping. Anesthesia was induced with thiopental or etomidate and maintained with oxygen, nitrous oxide, isoflurane, fentanyl, and vecuronium. Hemodynamic measurements included heart rate, systolic and diastolic blood pressure, cardiac output, systolic and diastolic pulmonary artery pressure, pulmonary capillary wedge pressure, central venous pressure, mixed venous oxygen saturation, electrocardiogram, and ST-T wave trend analysis. Demographic and clinical characteristics for the two groups were similar. Mixed venous oxygen saturation was significantly lower ( p < 0.05) in group N immediately after unclamping. There were no differences between groups for the other measurements studied. There were no episodes of myocardial ischemia in either group. This study demonstrates that amrinone provides equivalent hemodynamic control to SNP during abdominal aortic aneurysm surgery because it allows moderate reductions in blood pressure without affecting other hemodynamic measurements. Further studies are needed to assess whether patients with poor preoperative left ventricular function would benefit from amrinone management during AAA resection

Associations between ASA Physical Status and postoperative mortality at 48 h: a contemporary dataset analysis compared to a historical cohort

Abstract Background In this study, we examined the association between American Society of Anesthesiologists Physical Status (ASA PS) designation and 48-h mortality for both elective and emergent procedures in a large contemporary dataset (patient encounters between 2009 and 2014) and compared this association with data from a landmark study published by Vacanti et al. in 1970. Methods Patient history, hospital characteristics, anesthetic approach, surgical procedure, efficiency and quality indicators, and patient outcomes were prospectively collected for 732,704 consecutive patient encounters between January 1, 2009, and December 31, 2014, at 233 anesthetizing locations across 19 facilities in two US states and stored in the Quantum™ Clinical Navigation System (QCNS) database. The outcome (death within 48 h of procedure) was tabulated against ASA PS designations separately for patients with and without “E” status labels. To maintain consistency with the historical cohort from the landmark study performed by Vacanti et al. on adult men at US naval hospitals in 1970, we then created a comparison cohort in the contemporary dataset that consisted of 242,103 adult male patients (with/without E designations) undergoing elective and emergent procedures. Differences in the relationship between ASA PS and 48-h mortality in the historical and contemporary cohorts were assessed for patients undergoing elective and emergent procedures. Results As reported nearly five decades ago, we found a significant trend toward increased mortality with increasing ASA PS for patients undergoing both elective and emergent procedures in a large contemporary cohort (p < 0.0001). Additionally, the overall mortality rate at 48 h was significantly higher among patients undergoing emergent compared to elective procedures in the large contemporary cohort (1.27 versus 0.03 %, p < 0.0001). In the comparative analysis with the historical cohort that focused on adult males, we found the overall 48-h mortality rate was significantly lower among patients undergoing elective procedures in the contemporary cohort (0.05 % now versus 0.24 % in 1970, p < 0.0001) but not significantly lower among those undergoing emergent procedures (1.88 % now versus 1.22 % in 1970, p < 0.0001). Conclusions The association between increasing ASA PS designation (1–5) and mortality within 48 h of surgery is significant for patients undergoing both elective and emergent procedures in a contemporary dataset consisting of over 700,000 patient encounters. Emergency surgery was associated with a higher risk of patient death within 48 h of surgery in this contemporary dataset. These data trends are similar to those observed nearly five decades ago in a landmark study evaluating the association between ASA PS and 48-h surgical mortality on adult men at US naval hospitals. When a comparison cohort was created from the contemporary dataset and compared to this landmark historical cohort, the absolute 48-h mortality rate was significantly lower in the contemporary cohort for elective procedures but not significantly lower for emergency procedures. The underlying implications of these findings remain to be determined