John B. Leslie

Who is at risk for postdischarge nausea and vomiting after ambulatory surgery

Background: About one in four patients suffers from postoperative nausea and vomiting. Fortunately, risk scores have been developed to better manage this outcome in hospitalized patients, but there is currently no risk score for postdischarge nausea and vomiting (PDNV) in ambulatory surgical patients. Methods: We conducted a prospective multicenter study of 2,170 adults undergoing general anesthesia at ambulatory surgery centers in the United States from 2007 to 2008. PDNV was assessed from discharge until the end of the second postoperative day. Logistic regression analysis was applied to a development dataset and the area under the receiver operating characteristic curve was calculated in a validation dataset. Results: The overall incidence of PDNV was 37%. Logistic regression analysis of the development dataset (n = 1,913) identified five independent predictors (odds ratio; 95% CI): female gender (1.54; 1.22 to 1.94), age less than 50 yr (2.17; 1.75 to 2.69), history of nausea and/or vomiting after previous anesthesia (1.50; 1.19 to 1.88), opioid administration in the postanesthesia care unit (1.93; 1.53 to 2.43), and nausea in the postanesthesia care unit (3.14; 2.44–4.04). In the validation dataset (n = 257), zero, one, two, three, four, and five of these factors were associated with a PDNV incidence of 7%, 20%, 28%, 53%, 60%, and 89%, respectively, and an area under the receiver operating characteristic curve of 0.72 (0.69 to 0.73). Conclusions: PDNV affects a substantial number of patients after ambulatory surgery. We developed and validated a simplified risk score to identify patients who would benefit from long-acting prophylactic antiemetics at discharge from the ambulatory care center.

Characterization of prothrombin activation during cardiac surgery by hemostatic molecular markers.

BackgroundProthrombin activation represents the key regulatory step in the hemostatic process. Once formed, thrombin contributes to the generation of fibrin as well as the activation of platelets and fibrinolysis. Failure to suppress thrombin formation during cardiac surgery could result in disorders of hemostasis and thrombosis in the perioperative period. The aim of this study was to determine the time course for prothrombin activation during the perioperative period associated with cardiac surgery. MethotdsWe measured prothrombin activation during the perioperative period in 19 adult patients undergoing primary cardiac surgery using enzyme-linked immunosorbent assays for the detection of thrombin formation (prothrombin fragment 1.2 and thrombin-antithrombin III complex) and thrombin activity (fibrinopeptide A and fibrin monomer). Blood samples were obtained preoperatively; at 30-min intervals during cardiopulmonary bypass (CPB); and 1, 3, and 20 h after completion of CPB. ResultsDespite anticoagulation with heparin, plasma concentrations of prothrombin fragment 1.2, thrombin-antithrombin III complex, and fibrin monomer increased throughout CPB. Peak concentrations for all hemostatic markers occurred in the samples obtained 3 h after completion of CPB. By the morning after surgery, plasma prothrombin fragment 1.2 returned to preoperative concentrations; however, fibrinopeptide A and fibrin monomer concentrations remained significantly increased (P < 0.05) compared to preoperative values. ConclusionsThese data clearly demonstrate the occurrence of prothrombin activation and thrombin activity during CPB despite heparin concentrations adequate to maintain the activated clotting time greater than 400 s. Hemostatic markers for the activation of prothrombin demonstrated peak concentrations 3 h after completion of CPB with a return to baseline concentrations by the morning after surgery. Markers for thrombin activity, however, suggest the presence of active thrombin through the morning after surgery. Further investigations will be necessary to determine the role of hemostatic activation in thrombotic complications after cardiac surgery.

The effects of epsilon-aminocaproic acid on fibrinolysis and thrombin generation during cardiac surgery.

Despite the efficacy of antifibrinolytic drugs in reducing bleeding after cardiac surgery, concerns remain regarding their potential to promote thrombosis.We examined the effect of the antifibrinolytic drug, epsilon-aminocaproic acid (EACA) on fibrinolysis and thrombin generation during cardiac surgery. Forty-one adults undergoing primary coronary artery bypass graft surgery requiring cardiopulmonary bypass (CPB) were prospectively randomized in a double-blind trial to receive either saline or EACA. A loading dose of 150 mg/kg EACA was given before anesthetic induction, followed by a 15 mg [center dot] kg-1 [center dot] h-1 infusion, which continued until 3 h after CPB. Plasma samples for the measurement of D-dimer, thrombin-antithrombin III, and soluble fibrin were obtained before surgery, 1 h on CPB, and 3 and 20 h after CPB. In the EACA group, fibrinolytic activity, as measured by D-dimer, was significantly decreased 3 h after CPB, (0.51 +/- 0.15 mg/L vs 1.13 +/- 0.14 mg/L, P < 0.005). Decreased fibrinolytic activity was accompanied by decreased bleeding in the EACA group (660 +/- 127 mL vs 931 +/- 113 mL, P < 0.05). No differences in the generation of thrombin or soluble fibrin were apparent between the two groups. Suppression of fibrinolytic activity in the absence of concomitant reductions in thrombin generation suggests that EACA could potentiate a hypercoagulable prethrombotic state in the perioperative setting. Implications: In a randomized, prospective trial of primary cardiac surgery, we demonstrated that the synthetic antifibrinolytic drug epsilon-aminocaproic acid suppresses fibrinolysis with no effects on thrombin generation. These results suggest the potential for synthetic antifibrinolytic drugs to induce a hypercoagulable prethrombotic state in the perioperative setting. (Anesth Analg 1997;85:1221-6)

Peripherally Acting Mu-Opioid Receptor Antagonists and Postoperative Ileus: Mechanisms of Action and Clinical Applicability

Postoperative ileus (POI), a transient cessation of coordinated bowel function after surgery, is an important health care problem. The etiology of POI is multifactorial and related to both the surgical and anesthetic pathways chosen. Opioids used to manage surgical pain can exacerbate POI, delaying gastrointestinal (GI) recovery. Peripherally acting mu-opioid receptor (PAM-OR) antagonists are designed to mitigate the deleterious effects of opioids on GI motility. This new class is investigational for POI management with the goal of accelerating the recovery of upper and lower GI tract function after bowel resection. In this review, we summarize the mechanisms by which POI occurs and the role of opioids and opioid receptors in the enteric nervous system, discuss the mechanism of action of PAM-OR antagonists, and review clinical pharmacology and Phase II/III POI trial results of methylnaltrexone and alvimopan. Finally, the role of anesthesiologists in managing POI in the context of a multimodal approach is discussed.

Epidural narcotics in volunteers: Sensitivity to pain and to carbon dioxide

&NA; Tolerance to pain and sensitivity to rising concentrations fo inhaled carbon dioxide were measured before and after administration of metadone, 5 mg, or hydromorphone, 0.5 mg, by the intravenous route and by epidural injection in the lumbar or upper thoracic region in 5 subjects. Tolerance to periosteal pressure, cutaneous electrical stimulation and the cold pressor response to ice‐water immersion were measured in both upper and lower limbs. Tolerance to all three pain modalities was greater in the epidural “blocked” limbs than in the “unblocked” limbs or after intravenous administration, and this difference was sustained after a second injection of narcotic. Sensitivity to carbon dioxide was less depressed by epidural narcotic than by intravenous administration; however, after a second dose of narcotic, depression of CO2 sensitivity by epidural injection was comparable to that produced by intravenous injection. These observations support the hypothesis that epidural narcotics have a segmental action as well as a systematic effect, and that both actions are dose‐dependent.

Alvimopan for the Management of Postoperative Ileus

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, and administration of alvimopan, a peripherally acting μ-opioid receptor antagonist, in the management of postoperative ileus (POI). DATA SOURCES: A literature search (1980–October 2004%) applying the terms alvimopan, ADL 8–2698, and LY246736 was conducted using MEDLINE. Information was also obtained from scientific congress abstracts and data on file with the manufacturer. STUDY SELECTION AND DATA EXTRACTION: Studies and abstracts investigating alvimopan and POI were considered for inclusion; however, they were restricted to English-language articles. DATA SYNTHESIS: Alvimopan is a novel, peripherally acting μ-opioid receptor antagonist that is currently under evaluation for the management of POI. POI presents significant clinical challenges that can delay patient recovery and contribute to increased morbidity and prolonged hospitalization after surgery. Clinical trials have demonstrated that alvimopan, at oral doses of 6 and 12 mg, can accelerate time to recovery of gastrointestinal (GI) function and time to hospital discharge following abdominal surgery. The incidence of adverse events with alvimopan therapy was shown to be similar to that of placebo. CONCLUSIONS: Alvimopan is well tolerated and effective at accelerating GI recovery and time to discharge in patients who have undergone bowel resection or hysterectomy when administered prior to surgery and twice daily thereafter until discharge or for up to 7 days. Alvimopan potentially offers significant benefits for patients with POI over currently available treatments.

The role of neurokinin-1 receptor antagonists for the management of postoperative nausea and vomiting

Purpose of review To review the characteristics of neurokinin-1 receptor antagonists and their potential role in the management of postoperative nausea and vomiting. Recent findings Neurokinin-1 antagonists compete with substance P, an endogenous ligand with a high density of receptors in the area postrema and the nucleus tractus solitarii, believed to be involved in terminal emetic pathways. Experimental data provide evidence for efficacy against a wide range of peripheral and central emetic stimuli and clinical trials confirm that neurokinin-1 antagonists have significantly higher efficacy against vomiting than all other antiemetics, with relative risk reductions of over 50%. In fact, aprepitant – the first neurokinin-1 antagonist approved by the US Food and Drug Administration – provides superior protection against postoperative vomiting compared with ondansetron, and the same appears to be true for other drugs of this class. However, efficacy against nausea does not appear to be superior to other antiemetics, so that composite outcomes that are driven by nausea (e.g. complete response) disguise the unique anti-vomiting efficacy. Summary Postoperative vomiting can lead to rare but serious complications. Neurokinin-1 receptor antagonists are significantly more efficacious against postoperative vomiting than other antiemetics. Because the benefit in terms of absolute risk reduction is critically dependent on the patients baseline risk, it is recommended to use a validated risk score to identify patients who will benefit most from prophylaxis using neurokinin-1 receptor antagonists.

Attenuation of the hemodynamic responses to endotracheal intubation with preinduction intravenous labetalol

Endotracheal intubation following anesthesia induction frequently produces hypertension and tachycardia. This study evaluated the efficacy of preinduction IV labetalol for attenuating the hemodynamic responses to intubation following thiopental and succinylcholine induction of anesthesia. Two hours after diazepam (10 mg by mouth), 60 patients were randomized in a double-blind manner and received IV saline or labetalol at doses of 0.25, 0.5, 0.75, or 1 mg/kg in a parallel design study. Five minutes later, thiopental (4 mg/kg) and succinylcholine (1 mg/kg) were administered, and the trachea was intubated in 2 minutes. Nitrous oxide (70%) anesthesia was maintained for 10 minutes. Hemodynamic parameters were grouped and analyzed for significance (p less than 0.05) by two-way repeated measures analysis of variance and t-test with Bonferroni adjustments. Baseline group demographics and hemodynamics were comparable. All doses of labetalol significantly attenuated the rate-pressure product increase immediately postintubation versus placebo. There was a dose-dependent attenuation of the increases in heart rate and the systolic, diastolic, and mean blood pressures versus placebo following intubation. IV labetalol at doses up to 0.75 mg/kg offers an effective pharmacologic means of attenuating preoperative hemodynamic responses to endotracheal intubation.

Atrial natriuretic peptide plasma levels during cardiac surgery

In this investigation, the hypothesis was tested that patients with valvular heart disease have higher atrial natriuretic peptide (ANP) plasma levels than patients with coronary artery disease during cardiac surgery. Six patients scheduled for valve replacement (group V) and seven scheduled for coronary artery bypass grafting (CABG) (group C) were studied. ANP plasma levels and hemodynamic measurements were obtained at several times during surgery. ANP levels were elevated in both groups compared to those measured in healthy volunteers; and ANP levels in valvular patients were found to be higher than in the CABG patients. In addition, isotonic fluid loading, rewarming during cardiopulmonary bypass, and weaning from cardiopulmonary bypass increased ANP from baseline in group C. Mean arterial pressure and ANP levels correlated in group C. Ejection fraction, pulmonary artery diastolic pressure, and right atrial pressure did not correlate with ANP levels in either group. In conclusion, patients with valvular heart disease have higher ANP levels during surgery compared to patients with coronary artery disease. This difference probably relates to different pressure and volume loads on atrial tissue.

Anesthetic Routines: The Anesthesiologist's Role in GI Recovery and Postoperative Ileus

All patients undergoing bowel resection experience postoperative ileus, a transient cessation of bowel motility that prevents effective transit of intestinal contents or tolerance of oral intake, to varying degrees. An anesthesiologist plays a critical role, not only in the initiation of surgical anesthesia, but also with the selection and transition to effective postoperative analgesia regimens. Attempts to reduce the duration of postoperative ileus have prompted the study of various preoperative, perioperative, and postoperative regimens to facilitate gastrointestinal recovery. These include modifiable variables such as epidural anesthesia and analgesia, opioid-sparing anesthesia and analgesia, fluid restriction, colloid versus crystalloid combinations, prokinetic drugs, and use of the new peripherally acting mu-opioid receptor (PAM-OR) antagonists. Review and appropriate adaptation of these multiple modifiable interventions by anesthesiologists and their surgical colleagues will facilitate implementation of a best-practice management routine for bowel resection procedures that will benefit the patient and the healthcare system.