Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE-2).

BACKGROUND: In the POISE-2 (PeriOperative ISchemic Evaluation 2) trial, perioperative aspirin did not reduce cardiovascular events, but increased major bleeding. There remains uncertainty regarding the effect of perioperative aspirin in patients undergoing vascular surgery. The aim of this substudy was to determine whether there is a subgroup effect of initiating or continuing aspirin in patients undergoing vascular surgery. METHODS: POISE-2 was a blinded, randomized trial of patients having non-cardiac surgery. Patients were assigned to perioperative aspirin or placebo. The primary outcome was a composite of death or myocardial infarction at 30 days. Secondary outcomes included: vascular occlusive complications (a composite of amputation and peripheral arterial thrombosis) and major or life-threatening bleeding. RESULTS: Of 10 010 patients in POISE-2, 603 underwent vascular surgery, 319 in the continuation and 284 in the initiation stratum. Some 272 patients had vascular surgery for occlusive disease and 265 had aneurysm surgery. The primary outcome occurred in 13·7 per cent of patients having aneurysm repair allocated to aspirin and 9·0 per cent who had placebo (hazard ratio (HR) 1·48, 95 per cent c.i. 0·71 to 3·09). Among patients who had surgery for occlusive vascular disease, 15·8 per cent allocated to aspirin and 13·6 per cent on placebo had the primary outcome (HR 1·16, 0·62 to 2·17). There was no interaction with the primary outcome for type of surgery (P = 0·294) or aspirin stratum (P = 0·623). There was no interaction for vascular occlusive complications (P = 0·413) or bleeding (P = 0·900) for vascular compared with non-vascular surgery. CONCLUSION: This study suggests that the overall POISE-2 results apply to vascular surgery. Perioperative withdrawal of chronic aspirin therapy did not increase cardiovascular or vascular occlusive complications. Registration number: NCT01082874 ( http://www.clinicaltrials.gov).

Effect of intraoperative hyperoxia on the incidence of surgical site infections: a meta-analysis.

BACKGROUND: Whether supplemental intraoperative oxygen reduces surgical site infections remains unclear. Recent recommendations from the World Health Organization and Center for Disease Control to routinely use high inspired oxygen concentrations to reduce infection risk have been widely criticized. We therefore performed a meta-analysis to evaluate the influence of inspired oxygen on infection risk, including a recent large trial. METHODS: A systematic literature search was performed. Primary analysis included all eligible trials. Sensitivity analyses distinguished studies of colorectal and non-colorectal surgeries, and excluded studies with high risk of bias. Another post-hoc sensitivity analysis excluded studies from one author that appear questionable. RESULTS: The primary analysis included 26 trials (N=14,710). The RR [95%CI] for wound infection was 0.81 [0.70, 0.94] in the high vs. low inspired oxygen groups. The effect remained significant in colorectal patients (N=10,469), 0.79 [0.66, 0.96], but not in other patients (N=4,241), 0.86 [0.69, 1.09]. When restricting the analysis to studies with low risk of bias, either by strict inclusion criteria (N=5,047) or by researchers' judgment (N=12,547), no significant benefit remained: 0.84 [0.67, 1.06] and 0.89 [0.76, 1.05], respectively. CONCLUSIONS: When considering all available data, intraoperative hyperoxia reduced wound infection incidence. However, no significant benefit remained when analysis was restricted to objective- or investigator-identified low-bias studies, although those analyses were not as well-powered. Meta-analysis of the most reliable studies does not suggest that supplemental oxygen substantively reduces wound infection risk, but more research is needed to fully answer this question.

Circulating-water garment or the combination of a circulating-water mattress and forced-air cover to maintain core temperature during major upper-abdominal surgery.

BACKGROUND: A recent heat-balance study in volunteers suggested that greater efficacy of circulating-water garments (CWGs) results largely from increased heat transfer across the posterior skin surface since heat transfer across the anterior skin surface was similar with circulating-water and forced-air. We thus tested the hypothesis that the combination of a circulating-water mattress (CWM) and forced-air warming prevents core temperature reduction during major abdominal surgery no worse than a CWG does. METHODS: Fifty adult patients aged between 18 and 85 yr old, undergoing major abdominal surgery, were randomly assigned to intraoperative warming with a combination of forced-air and a CWM or with a CWG (Allon ThermoWrap). Core temperature was measured in the distal oesophagus. Non-inferiority of the CWM to the CWG on change from baseline to median intraoperative temperature was assessed using a one-tailed Student's t-test with an equivalency buffer of -0.5°C. RESULTS: Data analysis was restricted to 16 CWG and 20 CWM patients who completed the protocol. Core temperature increased in both groups during the initial hours of surgery. We had sufficient evidence (P=0.001), to conclude that the combination of a CWM and forced-air warming was non-inferior to a CWG in preventing temperature reduction, with mean (95% CI) difference in the temperature change between the CWM and the CWG groups (CWM-CWG) of 0.46°C (-0.09°C, 1.00°C). CONCLUSIONS: The combination of a CWM and forced-air warming is significantly non-inferior in maintaining intraoperative core temperature than a CWG. TRIAL REGISTRY: This trial has been registered at clinical trials.gov, identifier: NCT 00651898.

Effect of nasal cannula oxygen administration on oxygen concentration at facial and adjacent landmarks.

An oxygen-enriched atmosphere enhances the potential for operating-room fires. We thus determined oxygen concentrations at various facial landmarks during oxygen administration via nasal cannulae. Thirteen supine volunteers were draped similarly to patients undergoing a cervical-node biopsy. Oxygen was delivered in random order through nasal cannulae at rates of 2, 4, and 6 l x min(-1). Oxygen concentration was measured at pre-determined facial landmarks and also distal to the drape at non-facial sites. At a flow of 2 l x min(-1), oxygen concentrations exceeded 23% only within a few centimetres of the nasal cannula. Concentration increased as a function of flow, but rarely exceeded 26%. At all flow rates, concentrations distal to the drape were < 24%. To reduce combustion risk, ignition sources should be kept at least 10 cm from the oxygen outlet when using nasal cannula at a flow rate > or = 4 l x min(-1).

Deliberate mild hypothermia.

Core body temperature is normally rigidly regulated by effective thermoregulatory responses that are triggered by small deviations in core and skin temperature. All general anesthetics so far tested markedly impair thermoregulatory control, increasing the range of temperatures not triggering protective responses by approximately 20-fold. Inhibition of thermoregulatory control--and reemergence of protective responses--are major factors influencing intraoperative temperature. Mild hypothermia provides dramatic protection against cerebral ischemia and therefore is frequently indicated during neurosurgery. Hypothermia to core temperatures near 34 degrees C can usually be instituted passively so long as thermoregulatory vasoconstriction is inhibited by sufficient anesthesia or neurosurgery per se. When core temperature must be rapidly reduced, or reduced to values approaching 32 degrees C, active cooling will usually be needed. Forced air appears to be the most effective clinically practical cooling method. Mild hypothermia is also associated with serious complications including myocardial ischemia, impaired resistance to surgical wound infections, coagulopathies, and postoperative shivering. Consequently, patients deliberately made hypothermic during neurosurgery should subsequently be actively rewarmed.

Preanesthetic skin-surface warming reduces redistribution hypothermia caused by epidural block.

Redistribution of heat from the core to the cool peripheral compartments of the body causes hypothermia during epidural anesthesia. Diminishing the temperature gradient between the core and peripheral tissues by warming the body via the skin before anesthesia should prevent this hypothermia. We measured core temperature, skin temperatures, and cutaneous heat loss in seven volunteers who received two lidocaine epidural injections during a single study day. One epidural injection was given after the volunteer had rested in a cool room (approximately 22 degrees C) ("no prewarming") for 2 h, and one injection was given after the volunteer had been covered with a forced air warming mattress (approximately 38 degrees C) ("prewarming") for 2 h. Skin temperatures were higher after prewarming. The decrease in core temperature during epidural anesthesia was smaller after prewarming [mean within patient difference (prewarming-no prewarming): 0.41; P = 0.003]. However, heat loss was greater after prewarming (mean within patient difference: 26.4; P = 0.02). Shivering was less after prewarming. We conclude that prewarming decreases redistribution hypothermia caused by epidural block. These results support the hypothesis that redistribution of heat within the body, not heat loss, is the most important etiology of hypothermia from epidural anesthesia.

The analgesic efficacy of tramadol is impaired by concurrent administration of ondansetron.

Tramadol has weak opioid properties, and an analgesic effect that is mediated mainly by inhibition of the reuptake of norepinephrine and serotonin (5-hydroxytryptamine [5-HT]) and facilitation of 5-HT release (1,2) at the spinal cord. Because 5-HT3 receptors play a key role in pain transmission at the spinal level (3), the 5-HT3 antagonist ondansetron may decrease the efficacy of tramadol, as suggested in an abstract by Maroof et al. In that study, a small dose of 1 mg/kg tramadol was administered along with ondansetron 0.1 mg/kg or placebo, 15 min before the induction of anesthesia. Early postoperative pain scored differed significantly between the test groups. We therefore tested the hypothesis that the tramadol requirement by patient-controlled analgesia (PCA) may be increased when ondansetron is administered for antiemetic prophylaxis.

The effects of meperidine and sufentanil on the shivering threshold in postoperative patients. pascal.alfonsi@apr.ap-hop-paris.fr.

UNLABELLED: BACKGROUND. Meperidine (pethidine) reportedly treats postoperative shivering better than equianalgesic doses of other mu-receptor agonists. The authors' first goal was to develop a method to accurately determine postoperative shivering thresholds, and then to determine the extent to which meperidine and sufentanil inhibit postoperative shivering. METHODS: A computer-controlled infusion was started before operation in 30 patients, with target plasma concentrations of 0.15, 0.30, or 0.60 microg/ml meperidine or 0.1, 0.15, or 0.2 ng/ ml sufentanil targeted; patients were randomly assigned to each drug and concentration. The infusion was continued throughout surgery and recovery. Anesthesia was maintained with nitrous oxide and isoflurane. Core temperatures were approximately 34 degrees C by the end of surgery. The compensated core temperature at which visible shivering and a 20% decrease in steady-state oxygen consumption was recorded identified the shivering threshold. A blood sample for opioid concentration was obtained from each patient at this time. The ability of each opioid to reduce the shivering threshold was evaluated using linear regression. RESULTS: End-tidal isoflurane concentrations were <0.2% in each group at the time of extubation, and shivering occurred approximately 1 h later. Meperidine linearly decreased the shivering threshold: threshold (degrees C) = -2.8 x [meperidine (microg/ml)] + 36.2; r2 = 0.64, P = 0.0005. Sufentanil also linearly decreased the shivering threshold: threshold (degrees C) = -7.8 x [sufentanil (ng/ ml)] + 36.9; r2 = 0.46, P = 0.02. CONCLUSIONS: At a given dose, sufentanil inhibited shivering 2,800 times better than meperidine. However, the equianalgesic ratio of these drugs is approximately 4,900. That is, meperidine inhibited shivering better than would be expected based on the equianalgesic potency ratio. These data are thus consistent with clinical observations suggesting that meperidine indeed possesses special antishivering activity.

Opioids inhibit febrile responses in humans, whereas epidural analgesia does not: an explanation for hyperthermia during epidural analgesia.

BACKGROUND: Epidural analgesia is frequently associated with hyperthermia during labor and in the postoperative period. The conventional assumption is that hyperthermia is caused by the technique, although no convincing mechanism has been proposed. However, pain in the "control" patients is inevitably treated with opioids, which themselves attenuate fever. Fever associated with infection or tissue injury may then be suppressed by opioids in the "control" patients while being expressed normally in patients given epidural analgesia. The authors therefore tested the hypothesis that fever in humans is manifested normally during epidural analgesia, but is suppressed by low-dose intravenous opioid. METHODS: The authors studied eight volunteers, each on four study days. Fever was induced each day by 150 IU/g intravenous interleukin 2. Volunteers were randomly assigned to: (1) a control day when no opioid or epidural analgesia was given; (2) epidural analgesia using ropivacaine alone; (3) epidural analgesia using ropivacaine in combination with 2 microg/ml fentanyl; or (4) intravenous fentanyl at a target plasma concentration of 2.5 ng/ml. RESULTS: Fentanyl halved the febrile response to pyrogen, decreasing integrated core temperature from 7.0 +/- 3.2 degrees C. h on the control day, to 3.8 +/- 3.0 degrees C. h on the intravenous fentanyl day. In contrast, epidural ropivacaine and epidural ropivacaine-fentanyl did not inhibit fever. The fraction of core-temperature measurements that exceeded 38 degrees C was halved by intravenous fentanyl, and the fraction exceeding 38.5 degrees C was reduced more than fivefold. CONCLUSIONS: These data support the authors' proposed mechanism for hyperthermia during epidural analgesia. Fever during epidural analgesia should thus not be considered a complication of the anesthetic technique per se.

Induction of anesthesia with ketamine reduces the magnitude of redistribution hypothermia.

UNLABELLED: Hypothermia after induction of general anesthesia results largely from core-to-peripheral redistribution of body heat. Both central inhibition of tonic thermoregulatory vasoconstriction in arteriovenous shunts and anesthetic-induced arteriolar and venous dilation contribute to this redistribution. Ketamine, unique among anesthetics, increases peripheral arteriolar resistance; in contrast, propofol causes profound venodilation that other anesthetics do not. We therefore tested the hypothesis that induction of anesthesia with ketamine causes less core hypothermia than induction with propofol. Twenty patients undergoing elective surgery were randomly assigned to anesthetic induction with either 1.5 mg/kg ketamine (n = 10) or 2.5 mg/kg propofol (n = 10). Anesthesia in both groups was subsequently maintained with sevoflurane and 60% nitrous oxide in oxygen. Forearm minus finger, skin-temperature gradients <0 degrees C were considered indicative of significant arteriovenous shunt vasodilation. Ketamine did not cause vasodilation just after induction, whereas propofol rapidly induced vasodilation. Core temperatures in the patients given ketamine remained significantly greater than those in the patients induced with propofol. These data suggest that maintaining vasoconstriction during induction of anesthesia reduces the magnitude of redistribution hypothermia. IMPLICATIONS: Core hypothermia during the first hour of anesthesia was less after induction of anesthesia with ketamine than propofol. Maintaining arteriovenous shunt vasoconstriction during induction of anesthesia reduces the magnitude of redistribution hypothermia.

Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting, analgesic requirement, and sympathoadrenal responses.

BACKGROUND: In a controlled and double-blind study, the authors tested the hypothesis that preoperative insertion of intradermal needles at acupoints 2.5 cm from the spinal vertebrae (bladder meridian) provide satisfactory postoperative analgesia. METHODS: The authors enrolled patients scheduled for elective upper and lower abdominal surgery. Before anesthesia, patients undergoing each type of surgery were randomly assigned to one of two groups: acupuncture (n = 50 and n = 39 for upper and lower abdominal surgery, respectively) or control (n = 48 and n = 38 for upper and lower abdominal surgery, respectively). In the acupuncture group, intradermal needles were inserted to the left and right of bladder meridian 18-24 and 20-26 in upper and lower abdominal surgery before induction of anesthesia, respectively. Postoperative analgesia was maintained with epidural morphine and bolus doses of intravenous morphine. Consumption of intravenous morphine was recorded. Incisional pain at rest and during coughing and deep visceral pain were recorded during recovery and for 4 days thereafter on a four-point verbal rating scale. We also evaluated time-dependent changes in plasma concentrations of cortisol and catecholamines. RESULTS: Starting from the recovery room, intradermal acupuncture increased the fraction of patients with good pain relief as compared with the control (P < 0.05). Consumption of supplemental intravenous morphine was reduced 50%, and the incidence of postoperative nausea was reduced 20-30% in the acupuncture patients who had undergone either upper or lower abdominal surgery (P < 0.01). Plasma cortisol and epinephrine concentrations were reduced 30-50% in the acupuncture group during recovery and on the first postoperative day (P < 0.01). CONCLUSION: Preoperative insertion of intradermal needles reduces postoperative pain, the analgesic requirement, and opioid-related side effects after both upper and lower abdominal surgery. Acupuncture analgesia also reduces the activation of the sympathoadrenal system that normally accompanies surgery.

Postoperative pain and subcutaneous oxygen tension.

Surgical patients randomly assigned to standard pain control had postoperative subcutaneous oxygen partial pressures that were significantly less than patients given better pain treatment. Our data suggest that control of postoperative pain is a major determinant of surgical-wound infection and should be given the same consideration as maintaining adequate vascular volume and normothermia.

Postoperative pain facilitates nonthermoregulatory tremor.

BACKGROUND: Spontaneous tremor is relatively common in normothermic patients after operation and has been attributed to many causes. The hypothesis that nonthermoregulatory shivering-like tremor is facilitated by postoperative pain was tested. In addition, the effects of intravenous lidocaine on nonthermoregulatory tremor were evaluated. METHODS: Patients undergoing knee surgery were anesthetized with 2 microg/kg intravenous fentanyl and 0.2 mg/kg etomidate. Anesthesia was maintained with 1.7 +/- 0.8% (mean +/- SD) isoflurane. Intraoperative forced-air heating maintained normothermia The initial 44 patients were randomly allocated to receive an intra-articular injection of 20 ml saline (n = 23) or lidocaine, 1.5% (n = 21). The subsequent 30 patients were randomly allocated to receive an intravenous bolus of 250 microg/kg lidocaine followed by an infusion of 13 microg x kg(-1) x h(-1) lidocaine or an equivalent volume of saline when shivering was observed. Patient-controlled analgesia was provided for all patients: 3.5 mg piritramide, with a lockout interval of 5 min, for an unlimited total dose. Shivering was graded by a blinded investigator using a four-point scale. Pain was assessed by a 100-mm visual analog scale (0 = no pain and 100 = worst pain). The arteriovenous shunt status was evaluated with forearm-minus-fingertip skin-temperature gradients. RESULTS: Morphometric characteristics and hemodynamic responses were similar in the four groups. Core and mean skin temperature remained constant or increased slightly compared with preoperative values, and postoperative skin-temperature gradients were negative (indicating vasodilation) in nearly all patients. After intra-articular injection of saline, pain scores for the first postoperative hour averaged 46 +/- 32 mm (mean +/- SD), and 10 of the 23 (43%) patients shivered. In contrast, the pain scores of patients who received intra-articular lidocaine were significantly reduced to 5 +/- 9 mm and shivering was absent in this group (P < 0.05). In the second portion of the study, neither intravenous lidocaine nor saline reduced the magnitude or duration of nonthermoregulatory tremor or the patients' pain scores. CONCLUSIONS: Intra-articular, but not intravenous, lidocaine reduced surgical pain and prevented nonthermoregulatory shivering. Therefore, these data indicate that postoperative pain facilitates nonthermoregulatory shivering.