Kenneth J. Tuman

Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery.

To examine the interaction of epidural anesthesia, coagulation status, and outcome after lower extremity revascularization, 80 patients with atherosclerotic vascular disease were prospectively randomized to receive general anesthesia combined with postoperative epidural analgesia (GEN-EPI) or general anesthesia with on-demand narcotic analgesia (GEN). Demographics did not differ between groups except that the GEN-EPI group had a higher incidence of diabetes mellitus and of previous myocardial infarction. Coagulation status was monitored using thromboelastography. An additional 40 randomly selected patients without atherosclerotic vascular disease undergoing noncardiovascular procedures served as controls for coagulation status. Vascular surgical patients were hypercoagulable compared with control patients before operation and on the first postoperative day. Postoperatively, this hypercoagulability was attenuated in the GEN-EPI group and was associated with a lower incidence of thrombotic events (peripheral arterial graft coronary artery or deep vein thromboses). The rates of cardiovascular, infectious, and overall postoperative complications, as well as duration of intensive care unit stay, were significantly reduced in the GEN-EPI group. Stepwise logistic regression demonstrated that the only significant predictors of postoperative cardiovascular complications were preoperative congestive heart failure and general anesthesia without epidural analgesia. We conclude that in patients with atherosclerotic vascular disease undergoing arterial reconstructive surgery (a) thromboelastographic evidence of increased platelet-fibrinogen interaction is associated with early postoperative thrombotic events, and (b) epidural anesthesia and analgesia is associated with beneficial effects on coagulation status and postoperative outcome compared with intermittent on-demand opioid analgesia.

Preoperative airway assessment: Predictive value of a multivariate risk index

Using readily available and objective airway risk criteria, a multivariate model for stratifying risk of difficult endotracheal intubation was developed and its accuracy compared to currently applied clinical methods.We studied 10,507 consecutive patients who were prospectively assessed prior to general anesthesia with respect to mouth opening, thyromental distance, oropharyngeal (Mallampati) classification, neck movement, ability to prognath, body weight, and history of difficult tracheal intubation. After induction of anesthesia, the laryngeal view during rigid laryngoscopy was graded and the ability of experienced anesthesia personnel to ventilate via a mask was determined. Poor intubating conditions (laryngoscopy Grade IV) and inability to achieve adequate mask ventilation were identified in 107 (1%) and 8 (0.07%) cases, respectively. Logistic regression identified all seven criteria as independent predictors of difficulty with laryngoscopic visualization. A composite airway risk index (derived from nominalized odds ratios calculated from the multivariate model) as well a simplified (0 = low, 1 = medium, 2 = high) risk weighting exhibited higher positive predictive value for laryngoscopy Grade IV at scores with similar sensitivity to Mallampati class III, as well as higher sensitivity at scores with similar positive predictive value. Compared to Mallampati class I fewer false-negative predictions were observed at a risk index value of 0. We conclude that improved risk stratification for difficulty with visualization during rigid laryngoscopy (Grade IV) can be obtained by use of a simplified preoperative multivariate airway risk index, with better accuracy compared to oropharyngeal (Mallampati) classification at both low- and high-risk levels. (Anesth Analg 1996;82:1197-204)

Perioperative Oral Pregabalin Reduces Chronic Pain After Total Knee Arthroplasty: A Prospective, Randomized, Controlled Trial

BACKGROUND: Despite the enormous success of total knee arthroplasty (TKA), chronic neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established. We hypothesized that perioperative treatment with pregabalin, a chronic pain medication, would reduce the incidence of postsurgical neuropathic pain. METHODS: We performed a randomized, placebo-controlled, double-blind trial of pregabalin (300 mg) administered before TKA and for 14 days after TKA (150–50 mg twice daily). Patients were screened for the presence of neuropathic pain at 3 and 6 mo postoperatively using the Leeds Assessment of Neuropathic Symptoms and Signs scale. Secondary outcomes included postsurgical recovery and rehabilitation measures, including knee range of motion, opioid consumption, postoperative pain scores, sleep disturbance, and time to discharge as well as the occurrence of postoperative systemic complications. RESULTS: Of the 240 patients randomly assigned to the 2 treatment groups (120 in each), data for the primary outcome were obtained from 113 pregabalin patients and 115 placebo patients. At both 3 and 6 mo postoperatively, the incidence of neuropathic pain was less frequent in the pregabalin group (0%) compared with the placebo group (8.7% and 5.2% at 3 and 6 mo, respectively; P = 0.001 and P = 0.014). Patients receiving pregabalin also consumed less epidural opioids (P = 0.003), required less oral opioid pain medication while hospitalized (P = 0.005), and had greater active flexion over the first 30 postoperative days (P = 0.013). There were no differences in the actual recorded duration of hospitalization between the 2 groups, although time to achieve hospital discharge criteria was longer for placebo patients, 69.0 ± 16.0 h (mean ± sd), than that of pregabalin patients, 60.2 ± 15.8 h (P = 0.001). Sedation (P = 0.005) and confusion (P = 0.013) were more frequent on the day of surgery and postoperative day 1 in patients receiving pregabalin. CONCLUSION: Perioperative pregabalin administration reduces the incidence of chronic neuropathic pain after TKA, with less opioid consumption and better range of motion during the first 30 days of rehabilitation. However, in the doses tested, it is associated with a higher risk of early postoperative sedation and confusion.

Thromboelastography as an indicator of post-cardiopulmonary bypass coagulopathies

Postoperative hemorrhage in patients undergoing open-heart surgery is a major cause of morbidity and mortality. Monitoring of coagulation in these patients has routinely involved the activated clotting time. Thromboelastography is currently used as a monitor of coagulation during liver transplantation. The thromboelastogram, by providing information on the interaction of all the coagulation precursors, gives more clinically useful information on coagulation than that available from the coagulation profile or the activated clotting time alone. This study was done to assess the usefulness of thromboelastography in open-heart surgery. Thirty-eight patients (29 undergoing coronary artery bypass grafting and 9 undergoing valve replacement) were studied with activated clotting time, thromboelastography, and coagulation profiles during three periods: before bypass, during bypass, and after protamine administration. Thromboelastography was a significantly better predictor (87% accuracy) of postoperative hemorrhage and need for reoperation than was the activated clotting time (30%) or coagulation profile (51%). Thromboelastography is easy to use and provides diagnostic data within 30 minutes of blood sampling.

Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans.

Background: The central and peripheral inflammatory response to surgery may influence patient outcomes. This study examines the time course and clinical relevance of changes in prostaglandin E2 and cytokines in cerebrospinal fluid, local tissue (surgical site), and circulating blood during and after total hip replacement. Methods: Thirty osteoarthritis patients undergoing primary total hip arthroplasty with spinal anesthesia were randomly allocated to three groups (n = 10/group): placebo for 4 days before surgery and on the morning of surgery; placebo for 4 days before surgery and oral rofecoxib 50 mg on the morning of surgery; oral rofecoxib 50 mg for 4 days before surgery and the morning of surgery. Cerebrospinal fluid and plasma were collected before surgery and up to 30 h after incision for measurement of prostaglandin E2 and interleukins. When hip replacement was complete, a drain was placed in the hip wound and exudates were collected at 3 to 30 h after incision. Results: Cerebrospinal fluid showed an initial increase in interleukin 6 and a later rise in prostaglandin E2 concentration after surgery; interleukin 1&bgr; and tumor necrosis factor &agr; were undetectable. Hip surgical site fluid evidenced an increase in prostaglandin E2, interleukin 6, interleukin 8, and interleukin 1&bgr;; tumor necrosis factor &agr; decreased at 24 and 30 h. Preoperative administration of the cyclooxygenase 2 inhibitor rofecoxib reduced cerebrospinal fluid and surgical site prostaglandin E2 and cerebrospinal fluid interleukin 6. Cerebrospinal fluid prostaglandin E2 was positively correlated with postoperative pain and cerebrospinal fluid interleukin 6 with sleep disturbance. Poorer functional recovery was positively correlated with increased surgical site prostaglandin E2. Conclusions: These results suggest that upregulation of prostaglandin E2 and interleukin 6 at central sites is an important component of surgery induced inflammatory response in patients and may influence clinical outcome.

Effect of pulmonary artery catheterization on outcome in patients undergoing coronary artery surgery.

Previous studies have suggested that low-risk cardiac surgical patients may be safely managed without pulmonary artery catheterization (PAC). However, no prospective studies have determined whether PAC improves outcome in higher risk patients compared with that following central venous pressure (CVP) monitoring alone. The authors prospectively examined the incidence of and factors related to perioperative morbidity and mortality in 1094 consecutive patients undergoing coronary artery surgery managed with elective PAC (n = 537) or with CVP (n = 557). Perioperative risk factors and demographics that predict morbidity and mortality after cardiac surgery were used to quantify risk classification. Outcome was judged by length of ICU stay, occurrence of postoperative myocardial infarction, in-hospital death, major hemodynamic aberrations, and significant noncardiac systemic complications. No significant differences in any outcome variables were noted in any group of patients with similar quantitative risk classification managed with or without PAC, including those in the highest risk class. In addition, there were no significant differences in outcome among the 39 patients who would have been managed with CVP monitoring only, but who subsequently developed a clinical need for PAC based on the occurrence of serious hemodynamic events compared to patients who had PAC performed electively. This study suggests that PAC does not play a major role in influencing outcome after cardiac surgery, that even high-risk cardiac surgical patients may be safely managed without routine PAC, and that delaying PAC until a clinical need develops does not significantly alter outcome, but may have an important impact on cost savings.

Does Choice of Anesthetic Agent Significantly Affect Outcome after Coronary Artery Surgery

A prospective study of 1094 consecutive adult patients undergoing coronary revascularization was undertaken to determine the effect of anesthetic technique on outcome. Patients received one of five primary techniques: high-dose fentanyl (> 50 μg/kg), moderate-dose fentanyl (<50 μg/kg), sufentanil (3

Comparison of viscoelastic measures of coagulation after cardiopulmonary bypass.

Postoperative hemorrhage remains a major cause of morbidity after cardiopulmonary bypass (CPB). Treatment remains empiric because of the need for immediate correction and the lack of availability of rapid intraoperative coagulation monitoring (except for ACT) at most institutions. Thrombelastography (TEG) and Sonoclot analysis (SCT) are measures of viscoelastic properties of blood which allow rapid intraoperative evaluation of coagulation factor and platelet activity as well as overall clot integrity from a single blood sample. Routine coagulation tests (RCT) including activated clotting time (ACT), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen level (FIB), and platelet count (PLT) were determined and compared to TEG and SCT to assess which best predicted clinical hemostasis after CPB. Forty-two patients prospectively felt to be at high risk for excessive post-CPB bleeding had blood obtained for RCT, TEG, and SCT analysis before systemic heparinization and 30 min after protamine administration. Nine of 42 patients had excessive chest tube drainage, but no reoperations were required. After CPB, mean values for RCT were normal, but there were abnormalities in TEG and SCT parameters that reflect platelet-fibrin interaction. Both TEG and SCT were 100% accurate in predicting bleeding in these nine patients and, overall, both tests were significantly better predictors of postoperative hemorrhage than RCT. We conclude that viscoelastic determinants of clot strength may be abnormal after CPB and that SCT and TEG are, therefore, more useful than RCT for the detection and management of coagulation defects associated with CPB.

Effects of Progressive Blood Loss on Coagulation as Measured by Thrombelastography

The effects of progressive blood loss on coagulation were studied in 87 adults (age 23–66 yr) undergoing a variety of operations under general anesthesia. None had preoperative alterations in coagulation or liver function and none were receiving anticoagulant or antiplatelet medication. Whole blood coagulation status was quantitated using thrombelastography (TEG). Blood samples for TEG were obtained 5 min before and 15 min after induction of anesthesia, after each increment of blood loss (EBL) equalling 5% of estimated blood volume (EBV), at the end of surgery, and 2 hr postoperatively. Patients with EBL exceeding 0.15 EBV were given packed red cells and crystalloid solution. Patients with EBL less than 0.15 EBV received only crystalloid. Thrombelastography analysis showed a trend toward increased coagulability with progressive blood loss. Two of four patients with 80% loss of EBV maintained normal to enhanced coagulation status, although the other two developed clinical and thrombelastographic evidence of coagulopathy. Thrombelastography allowed rapid intraoperative diagnosis and specific treatment of loss of platelet activity in the latter two patients. We conclude that during moderate to massive blood loss, use of supplemental fresh frozen plasma and/or platelets should be reserved for patients with documented defects in coagulation. Thrombelastography is useful for the detection and management of coagulation defects associated with intraoperative blood loss.

Intrathecal magnesium prolongs fentanyl analgesia: A prospective, randomized, controlled trial

Magnesium is a noncompetitive, N-methyl-d-aspartate receptor antagonist that does not effectively cross the blood-brain barrier when given IV. Intrathecal magnesium potentiates opioid antinociception in rats, and the safety of intrathecal magnesium has been demonstrated in animals. This is the first prospective human study evaluating whether intrathecal magnesium could prolong spinal opioid analgesia. Fifty-two patients requesting analgesia for labor were randomized to receive either intrathecal fentanyl 25 &mgr;g plus saline or fentanyl 25 &mgr;g plus magnesium sulfate 50 mg as part of a combined spinal-epidural technique. The duration of analgesia of the intrathecal drug combination was defined by the time of patient request for additional analgesia. There was significant prolongation in the median duration of analgesia (75 min) in the magnesium plus fentanyl group compared with the fentanyl alone group (60 min). There was no associated increase in adverse events in the group that received intrathecal magnesium. Larger doses of intrathecal magnesium were not studied in this group of patients because of the limitations on cephalad spread when hyperbaric solutions are injected in the sitting position. Our data indicate that intrathecal magnesium prolongs spinal opioid analgesia in humans and suggest that the availability of an intrathecal N-methyl-d-aspartate antagonist could be of clinical importance for pain management.