Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

Neuraxial block, death and serious cardiovascular morbidity in the POISE trial.

BACKGROUND: This post hoc analysis aimed to determine whether neuraxial block was associated with a composite of cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal cardiac arrest within 30 days of randomization in POISE trial patients. METHODS: A total of 8351 non-cardiac surgical patients at high risk of cardiovascular complications were randomized to ß-blocker or placebo. Neuraxial block was defined as spinal, lumbar or thoracic epidural anaesthesia. Logistic regression, with weighting using estimated propensity scores, was used to determine the association between neuraxial block and primary and secondary outcomes. RESULTS: Neuraxial block was associated with an increased risk of the primary outcome [287 (7.3%) vs 229 (5.7%); odds ratio (OR), 1.24; 95% confidence interval (CI), 1.02-1.49; P=0.03] and MI [230 (5.9%) vs 177 (4.4%); OR, 1.32; 95% CI, 1.07-1.64; P=0.009] but not stroke [23 (0.6%) vs 32 (0.8%); OR, 0.76; 95% CI, 0.44-1.33; P=0.34], death [96 (2.5%) vs 111 (2.8%); OR, 0.87; 95% CI, 0.65-1.17; P=0.37] or clinically significant hypotension [522 (13.4%) vs 484 (12.1%); OR, 1.13; 95% CI, 0.99-1.30; P=0.08]. Thoracic epidural with general anaesthesia was associated with a worse primary outcome than general anaesthesia alone [86 (12.1%) vs 119 (5.4%); OR, 2.95; 95% CI, 2.00-4.35; P<0.001]. CONCLUSIONS: In patients at high risk of cardiovascular morbidity, neuraxial block was associated with an increased risk of adverse cardiovascular outcomes, which could be causal or because of residual confounding.

Role of continuous positive airway pressure to the non-ventilated lung during one-lung ventilation with low tidal volumes.

INTRODUCTION: In multiple study populations large tidal volumes (8 - 12 ml/kg) have deleterious effects on lung function in multiple study populations. The accepted approach to hypoxemia during one-lung ventilation is the application of continuous positive airway pressure to the non-ventilated lung first, followed by application of positive end-expiratory pressure to the ventilated lung. To our knowledge the effectiveness of positive end-expiratory pressure or continuous positive airway pressure on maintaining PaO(2) with one-lung ventilation was not studied with smaller tidal volume (6ml/kg) ventilation. Our objective was to compare continuous positive airway pressure of 5 cm H(2)O or positive end-expiratory pressure of 5 cm H(2)O during small tidal volume one-lung ventilation. METHODS: Thirty patients undergoing elective, open thoracotomy with one-lung ventilation were randomized to continuous positive airway pressure or positive end-expiratory pressure and then crossed over to the other modality.  RESULTS: There was a statistically significant higher PaO(2) (141±81.6 vs 112±48.7, p = 0.047) with continuous positive airway pressure than positive end-expiratory pressure while on one-lung ventilation. Two patients desaturated requiring 100% O(2) with both positive end-expiratory pressure and continuous positive airway pressure. On two occasions the surgeon requested the continuous positive airway pressure be discontinued due to lung inflation. CONCLUSION: The use of continuous positive airway pressure of 5 cm H(2)O to the non-ventilated lung while using small tidal volumes for one-lung ventilation improved PaO(2) when compared with positive end-expiratory pressure of 5 cm H(2)O to the ventilated lung.

Arterial pCO2 changes during thoracoscopic surgery with CO2 insufflation and one lung ventilation.

INTRODUCTION: The respiratory effects (changes in pH and PaCO(2)) of carbon dioxide insufflation in thoracoscopic surgery in adult patients with pulmonary disease were not documented previously. METHODS: In this observational study 21 patients scheduled for elective thoracoscopic surgery with one lung ventilation using a double lumen tube and intraoperative carbon dioxide insufflation were studied. Arterial blood gas findings were correlated with demographic and intraoperative variables. RESULTS: When compared to baseline (10-15 minutes of one lung ventilation before carbon dioxide insufflation), carbon dioxide insufflation lowered the pH, 7.31±0.08 vs 7.40±0.05 (p<0.001) caused increased PaCO(2), 53±12 vs 42±6.0 (p<0.001) at 40-60 minutes after carbon dioxide insufflation. These derangements in arterial blood gases persisted in the post-anesthetic care unit with pH 7.33±0.04 vs 7.40±0.05 (p<0.001) and PaCO(2) 51±6.7 vs 42±6.0 (p<0.001). Moderate hypercarbia defined as PaCO(2) >50 mmHg, developed in 12 of 21 patients (57%) and was associated to lower FEV1/FVC ratios 60±21 vs 81±3%, older age 69±9 vs 56±17 years, and history of smoking, 43 ± 30 vs 16±21 pack years, p<0.05. CONCLUSIONS: Intrathoracic carbon dioxide insufflation causes significant derangements in pH and PaCO(2) which is worse in patients with lower FEV1/FVC, increased age and smoking history.

Preoperative oral B vitamins prevent nitrous oxide-induced postoperative plasma homocysteine increases.

UNLABELLED: Nitrous oxide increases total homocysteine (tHcy) plasma levels, which are associated with an increase in perioperative myocardial ischemia. We designed this study to determine whether oral B vitamins, which are cofactors in homocysteine metabolism, can prevent nitrous oxide anesthesia-induced tHcy increases in patients undergoing elective surgery scheduled to last longer than 3 h. Fifty-three patients presenting for elective revision knee or hip arthroplasty received in random, double-blinded fashion oral vitamin B complex (folate 2.5 mg, B(6) 25 mg, and B(12) 500 microg) or placebo daily for 1 wk before surgery. Anesthesia was induced with propofol and maintained with an opioid, isoflurane, and nitrous oxide/oxygen (inspired nitrous oxide >50%). Blood samples for measurement of tHcy concentration were obtained at study enrollment, before induction, on arrival in the postanesthesia care unit, and on Day 5. Fourteen patients had their surgery rescheduled after taking their vitamins and were removed from the study. The Placebo group had a mean increase in tHcy concentration from baseline of 15% +/- 31% compared with the Vitamin group, which had an initial decrease of 9.1% +/- 11% (P = 0.035). This was maintained throughout the 5-day study period. The use of an oral B vitamin complex prevented the increase in postoperative tHcy by nitrous oxide. IMPLICATIONS: The use of nitrous oxide anesthesia increases postoperative homocysteine concentrations and associated myocardial ischemia. This study indicates that a 1-wk course of oral B vitamins can prevent the increase in homocysteine from nitrous oxide, and, by implication, myocardial ischemia as well.

Epidural analgesia reduces postoperative myocardial infarction: a meta-analysis.

UNLABELLED: Postoperative cardiac morbidity and mortality continue to pose considerable risks to surgical patients. Postoperative epidural analgesia is considered to have beneficial effects on cardiac outcomes. The use in high-risk cardiac patients remains controversial. No study has shown that postoperative epidural analgesia decreases postoperative myocardial infarction (PMI) or death. All studies are underpowered to show such a result, and the cost of conducting a large trial is prohibitive. We performed a metaanalysis to determine whether postoperative epidural analgesia continued for more than 24 h after surgery reduces PMI or in-hospital death. The available databases were searched for randomized controlled trials of epidural analgesia that was extended at least 24 h into the postoperative period. The search yielded 17 studies, of which 11 were randomized controlled trials comprising 1173 patients. Metaanalysis was conducted by using the fixed-effects model, calculating both an odds ratio and a rate difference. Postoperative epidural analgesia resulted in better analgesia for the first 24 h after surgery. The rate of PMI was 6.3%, with lower rates in the Epidural group (rate difference, -3.8%; 95% confidence interval [CI] -7.4%, -0.2%; P = 0.049). The frequency of in-hospital death was 3.3%, with no significant difference between Epidural and Nonepidural groups (rate difference, -1.3%; 95% CI, -3.8%, 1.2%, P = 0.091). Subgroup analysis of postoperative thoracic epidural analgesia showed a significant reduction in PMI in the Epidural group (rate difference, -5.3%; 95% CI, -9.9%, -0.7%; P = 0.04). IMPLICATIONS: Postoperative epidural analgesia, especially thoracic epidural analgesia, continued for more than 24 h reduces postoperative myocardial infarctions.

Nitrous oxide-induced increased homocysteine concentrations are associated with increased postoperative myocardial ischemia in patients undergoing carotid endarterectomy.

UNLABELLED: Nitrous oxide anesthesia causes increased postoperative plasma homocysteine levels. Acute increases in plasma homocysteine are associated with impaired endothelial function and procoagulant effects. This nitrous oxide-induced plasma homocysteine increase may therefore affect the risk of perioperative cardiovascular events. This prospective, randomized study was therefore designed to evaluate the effect of nitrous oxide anesthesia and postoperative plasma homocysteine levels on myocardial ischemia in patients undergoing carotid endarterectomy. After institutional review board approval and written informed consent, 90 ASA Class I-III patients presenting for elective carotid endarterectomy were randomized to receive general anesthesia with or without nitrous oxide. Prior to induction, on arrival in the postanesthesia care unit, and after 48 h, blood samples were obtained for homocysteine analysis. Three hours prior to induction and for 48 h postoperatively patients were monitored by a three-channel, seven-lead Holter monitor. Postoperatively in the postanesthesia care unit and at 48 h the nitrous oxide group had increased mean plasma homocysteine concentrations of 15.5 +/- 5.9 and 18.8 +/- 14.7 when compared with the nonnitrous group of 11.4 +/- 5.2 and 11.3 +/- 4.0 micromol/L, P: < 0.001. The nitrous oxide group had an increased incidence of ischemia (46% vs. 25%, P: < 0.05), significantly more ischemia (63 +/- 71 vs. 40 +/- 68 min, P: < 0.05), had more ischemic events (82 vs. 53, P: < 0.02), and had more ischemic events lasting 30 min (23 vs. 14, P: < 0.05) than the nonnitrous group. This study reconfirmed that intraoperative nitrous oxide is associated with postoperative increases in plasma homocysteine concentration. This was associated with an increase in postoperative myocardial ischemia. IMPLICATIONS: Use of nitrous oxide during carotid artery surgery induces increases in postoperative plasma homocysteine concentration and is associated with increases in postoperative myocardial ischemia.

The use of intraoperative nitrous oxide leads to postoperative increases in plasma homocysteine.

UNLABELLED: Hyperhomocysteinemia is an independent risk factor for coronary artery and cerebrovascular disease, but its significance in the perioperative period is unknown. Nitrous oxide inhibits methionine synthase, which aids in the conversion of homocysteine to methionine. In this prospective, controlled, randomized study, we determined the effect of intraoperative nitrous oxide exposure on postoperative plasma homocysteine concentrations. Twenty ASA physical status I-III patients, aged >18 yr, presenting for elective craniotomy, were randomized to receive general anesthesia with or without nitrous oxide (inspired nitrous oxide >50%). Plasma was sampled before the induction of anesthesia, on arrival in the postanesthesia care unit (PACU) after discontinuation of nitrous oxide, and 24 h after induction. There was a significant increase (22.6+/-11.4 vs 13.0+/-4.7 micromol/L; P = 0.0038 for postoperative versus preinduction values) in plasma homocysteine concentrations in the nitrous oxide group on arrival in the PACU and for 24 h. In the nonnitrous oxide group, mean plasma homocysteine concentrations did not change (9.5+/-1.9 vs 9.8+/-1.6 micromol/L; P = 0.86 for postoperative versus preinduction values). The change in plasma homocysteine concentrations in the nitrous oxide group was significantly different from that in the nonnitrous group (P = 0.0031). We conclude that the use of intraoperative nitrous oxide leads to significant increases in perioperative plasma homocysteine concentrations. IMPLICATIONS: Short-term exposure to nitrous oxide led to significant increases in plasma homocysteine. Further investigations are required to determine the clinical significance of this change.

Myocardial infarction after noncardiac surgery.

BACKGROUND: In this study, the authors intensively monitored isoenzyme and electric activity of the heart for the first 7 days after noncardiac surgery in a large group of patients at risk for postoperative myocardial infarction (PMI). METHODS: After institutional review board approval and written informed consent were received, 323 patients, aged 50 yr or older, who had ischemic heart disease and presented for noncardiac surgery, were enrolled in this prospective, blinded study. After operation, patients had daily clinical assessments, electrocardiograms, and measurements of creatine kinase (CK), CK-2 (mass and activity), and Troponin-T on the operative night, twice daily on postoperative days 1-4, and then daily on days 5-7. A diagnosis of PMI was made if the total CK was > 174 U/l and in the presence of two of the following: (1) CK-2/CK (mass or activity) > 5%, (2) new Q waves lasting > or = 0.04 s and 1 mm deep in at least two contiguous leads, (3) Troponin-T was > 0.2 microg/l, or (4) a positive result of pyrophosphate scan. RESULTS: Eighteen of the 323 patients (5.6%) had a PMI, of which 3 (17%) were fatal. Only 3 of 18 patients had chest pain, whereas 10 of 18 patients (56%) had other clinical findings. The electrocardiographic classification of the PMI was Q wave in 6, non-Q wave in 10, and indeterminate in 2. The PMIs occurred on the day of operation in 8, on day one in 6, on day two in 3, and on day four in 1 patient. CONCLUSIONS: This study determined that PMI was an early event, only occasionally associated with chest pain, and usually non-Q wave in nature.

Anaesthesia preadmission assessment: a new approach through use of a screening questionnaire.

PURPOSE: The preadmission assessment of patients one to two weeks preoperatively has become the standard across North America. We have devised a new approach that utilises a preoperative screening questionnaire, and this study attempted to determine the effectiveness of this technique. METHODS: Over six weeks, the attending anaesthetist for each patient undergoing non-cardiac surgery processed through the preadmission clinic (PAC) completed a study survey. This survey questioned if the assessment was appropriate with reasons, the consequences of no assessment, and if time was saved/lost on the day of surgery. RESULTS: Three hundred and seventy patients were processed (243 same-day (SD), 111 outpatient (O/P), and 16 inpatients (I/P)). Of these, 224 were assessed in the PAC (101 by medicine, 84 by anaesthesia and 39 by both): 42% (94) based on the questionnaire, 12% (26) due to consultation, and 46% (104) due to positive questionnaires and consultation. The physician assessments were appropriate 184/219 (84%) times, inappropriate in 35 (16%), while there was no answer for five. Assessments were inappropriate because 25/35 (71%) were unnecessary, while in nine (26%) the patient was not optimised. Of the patients not assessed in the PAC only 9/145 (6%) should have been assessed. CONCLUSION: The use of our screening tool in combination with direct referrals appropriately determines assessment needs of patients and allows for more efficient use of medical personnel in the PAC.

Addition of morphine to intra-articular bupivacaine does not improve analgesia following knee joint replacement.

BACKGROUND AND OBJECTIVES: In an effort to further decrease postoperative opioid requirements and improve analgesia in patients undergoing elective knee joint replacement, a study was made of the effectiveness of adding morphine to an intra-articular bupivacaine injection given immediately following surgery. METHODS: In random, double-blind fashion, 75 patients received a 31-mL intra-articular injection consisting of either 30 mL 0.5% bupivacaine with 1:200,000 epinephrine and 1 mL normal saline (group BUP), 30 mL 0.5% bupivacaine with 1:200,000 epinephrine and 1 mg (1 mL) preservative-free morphine (group BUP-MORPH), or 30 mL normal saline with 1:200,000 epinephrine and 1 mg preservative-free morphine (group MORPH). Postoperative analgesia was supplied by patient controlled analgesia (PCA) with morphine. Patients were assessed at 1, 2, 4, and 24 hours for pain (visual analog and verbal rating scales), morphine utilization, and side effects. Knee range of motion was measured before operation and at hospital discharge. RESULTS: There was no difference among the three groups in PCA morphine requirements, pain scores by either scale, range of motion, or incidence of side effects, including somnolence, urinary retention, nausea and vomiting, and pruritus. CONCLUSION: The addition of 1 mg morphine to an intra-articular injection of 30 mL 0.5% bupivacaine with 1:200,000 epinephrine given at wound closure does not improve analgesia in patients undergoing elective knee joint replacement.

Comparison of pulsatile versus nonpulsatile perfusion on the postcardiopulmonary bypass aortic-radial artery pressure gradient.

OBJECTIVE: To investigate whether the type of perfusion, pulsatile (PP) or nonpulsatile (NP), has any effect on the pressure gradient that exists between the aortic root and the radial artery after cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized study. SETTING: Tertiary care, university hospital. PARTICIPANTS: Eighty patients undergoing elective, hypothermic coronary artery bypass graft (CABG) surgery. INTERVENTIONS: Pulsatile perfusion with a pulse pressure of 10 to 20 mmHg and a frequency of 60 to 80 beats/min was created during the hypothermic phase of CPB. Both the radial artery and aorta were cannulated and attached to separate transducers but displayed and analyzed on the same monitor. MEASUREMENTS AND MAIN RESULTS: Simultaneous recordings of radial artery and aortic root blood pressure were made prebypass, during CPB, and after discontinuation of CPB at 2, 5, and 10 minutes. During CPB, the PP group had a significantly higher mean pulse pressure measured at the aortic root than the NP group (15.5 +/- 8.1 v 1.7 +/- 2.7, p < 0.0001). The aortic-to-radial-artery gradient within both groups was significantly different after CPB for systolic (SBP), diastolic (DBP), and mean pressure (MAP) (p < 0.0001). There were, however, no statistically significant differences between the PP and NP groups in the aortic-to-radial-artery gradient after CPB for either SBP, DBP, or MAP. CONCLUSIONS: Pulsatile perfusion had no effect on the aortic root radial artery blood pressure gradient after CPB in elective CABG surgery patients.

The addition of continuous intravenous infusion of ketorolac to a patient-controlled analgetic morphine regime reduced postoperative myocardial ischemia in patients undergoing elective total hip or knee arthroplasty.

This double-blind randomized trial assessed the effect of adding an intravenous continuous infusion of ketorolac to a patient-controlled analgesia (PCA) morphine regimen on analgesia, heart rate, arterial blood pressure, and postoperative myocardial ischemia. Patients having elective total hip or knee replacement were randomized to receive ketorolac 30 mg bolus, followed by an infusion of 5 mg/h for 24 h or placebo. All patients had access to PCA morphine (20 microg/kg bolus, with a lockout of 6 min). Patients were monitored for pain visual analog scale, blood pressure, heart rate, and ST segment depression via a continuous Holter monitor. ST depression of 1 mm 60 ms after the J point was considered significant if it lasted more than 1 min. There was no difference in demographics, risk factors, or cardiac medications between the groups. Ketorolac-treated patients had significantly better pain control at 2, 6, and 24 h. There was significant morphine sparing at all times after 3 h. There was no difference in the number of ischemic events between the groups. The ischemic episodes of the patients who received ketorolac occurred at slower heart rates (97 +/- 15 vs 114 +/- 16 bpm, P = 0.001) than those of patients in the placebo group. The duration of ST depression was shorter in ketorolac-treated patients (24 +/- 35 vs 76 +/- 95 min, P < 0.05). All ST depressions were clinically silent. Logistic regression of factors predicting ischemia included the use of calcium channel blockers and low pain score. These results suggest that analgesia with ketorolac reduces the duration of ischemic episodes in the first 24 h postoperatively.

Continuous epidural ropivacaine 0.2% for analgesia after lower abdominal surgery.

The purpose of this study was to determine whether a lumbar epidural infusion of ropivacaine 0.2% would provide effective analgesia with an acceptably low incidence of motor blockade and side effects after lower abdominal surgery. After combined general and epidural anesthesia and surgery, 125 patients were randomly assigned to receive either saline or ropivacaine 0.2% at a rate of 6, 8, 10, 12, or 14 mL/h (Groups R6, R8, R10, R12, and R14, respectively) for 21 h. Supplemental analgesia, if required, was provided with intravenous patient-controlled analgesia with morphine. Data were collected at 4, 8, and 21 h, and included morphine consumption, pain scores at rest and with coughing, motor and sensory block, and adverse events. Cumulative morphine consumption was less in Groups R10, R12, and R14 compared with the saline group. At 4 h analgesia was better among patients receiving ropivacaine, but at 21 h pain scores were identical. Sensory blockade at 8 and 21 h was greater in the ropivacaine groups compared with the saline group. Approximately 30% of R8, R10, and R12 patients, and 63% of R14 patients had demonstrable motor block of the lower limbs at 21 hours. We conclude that lumbar epidural ropivacaine 0.2% reduces parenteral morphine requirements but has little effect on pain scores and may be associated with motor blockade.

Patient attitudes regarding pca and associated costs.

PURPOSE: To determine patients' knowledge and attitudes towards patient-controlled analgesia (PCA) costs through the use of our acute pain service quality assurance (QA) programme. METHODS: Quality Assurance questionnaires were distributed to all patients receiving PCA opioids for > 12 hr. Patients were asked to note the presence of side effects (nausea/vomiting, pruritus, urinary retention), to indicate their satisfaction with regard to their pain relief, follow-up assessments, treatment of side effects, and to recall the previous method of pain relief and their satisfaction with it. Patients were also asked to estimate the total cost of PCA (0-$50, $50-100, $100-200, > $200), and what amount if any they would be willing to pay (0-$50, $50-100, $100-200, > $200). Results obtained over a recent four month period were reviewed. RESULTS: One hundred and thirty-three questionnaires were distributed and 103 (77%) were returned. The percentage of patients rating their satisfaction as very good or excellent was 86% for pain relief, 96% for follow-up, 71% for side effect treatment, but only 43% for their previous surgical pain relief (P < 0.001). The distribution of cost estimates was 10% $50-100, 37% $100-200 and 53% > $200 with 60% willing to pay a portion of this cost. Those willing to pay were more likely to have had very good or excellent pain relief (94% vs 71%, P < 0.05) and treatment of side effects (71% vs 48%, P < 0.05) than those not willing to pay. CONCLUSIONS: Patients continue to be highly satisfied with PCA therapy and are aware of the costs involved. A majority of patients were willing to pay to obtain this service if necessary. Patients who had poorer pain relief and less efficacious treatment of their side effects were less willing to pay.

Effect of varying intravenous patient-controlled analgesia dose and lockout interval while maintaining a constant hourly maximum dose.

STUDY OBJECTIVE: To investigate the effect on the use of intravenous patient-controlled analgesia (PCA) of varying the dose (D) and lockout interval (LI) while keeping the hourly maximum dose constant. DESIGN: Randomized, prospective study. SETTING: Teaching hospital. PATIENTS: 75 patients scheduled to receive PCA morphine following abdominal surgery. INTERVENTIONS: Postoperatively, patients were randomly assigned to receive PCA morphine with the following parameters: D = 1 mg, LI = 6 min (Group 1-6), D = 1.5 mg, LI = 9 min (Group 1.5-9), or D = 2 mg, LI = 12 min (Group 2-12), so that each group could receive a maximum hourly dose or 10 mg. Inadequate analgesia was managed by increasing the dose and lockout interval, while excessive sedation or respiratory rate less than 10 breaths/min resulted in decreasing the dose and lockout interval. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for pain [visual analog scale (VAS), verbal rating scale (VRS)] and side effects at 1, 2, 4, and 24 hours. The number of doses administered, missed attempts, and morphine used for the first 24 hours was recorded by automatic printout from the PCA machine. There was no difference in the total 24-hour morphine consumption, analgesia, or incidence of side effects among the three groups at any of the measurement times. Two patients, one each in the 1.5-9 and 2-12 groups, required naloxone for respiratory depression. The number of PCA injections, attempts, missed attempts, and the incidence of dosage adjustment were all significantly higher for the 1-6 group (p < 0.05). CONCLUSION: The use of 1.0 mg with a 6-minute lockout may represent appropriate dose titration because this group obtained equivalent analgesia, morphine use, and side effects as the two larger dose and lockout groups. However, the increased number of PCA attempts and missed attempts may reflect lower satisfaction with PCA therapy.

Intra-articular injection of bupivacaine in knee-replacement operations. Results of use for analgesia and for preemptive blockade.

The effectiveness of an intra-articular injection of bupivacaine, administered before the incision or after closure of the wound, was studied in an effort to decrease the need for postoperative narcotics and to improve analgesia for patients who have elective knee replacement. Eighty-two patients received two intra-articular injections in a random, double blind fashion. Twenty-eight of them received thirty milliliters of 0.5 percent bupivacaine and 1:200,000 epinephrine in saline solution before the incision and an injection of thirty milliliters of plain saline solution after closure of the wound (Group 1). Twenty-seven patients received an injection of thirty milliliters of plain saline solution before the incision and thirty milliliters of 0.5 percent bupivacaine and 1:200,000 epinephrine in saline solution after closure of the wound (Group 2). Twenty-seven patients were given thirty milliliters of plain saline solution (a placebo) for both injections (Group 3). The patients who had received bupivacaine after closure of the wound (Group 2) used less morphine from the patient-controlled analgesia pumps than the patients who had received bupivacaine before the incision (Group 1) and the patients who had received the placebo (Group 3). In the first twenty-four hours after the operation, the administration of morphine (mean and standard deviation) was 59 +/- 27 milligrams for Group 2 compared with 68 +/- 30 milligrams for Group 1 (p = 0.26) and 81 +/- 30 milligrams for Group 3 (p = 0.006). At the time of discharge from the hospital, the patients in Group 2 also had a significantly greater mean range of motion (85.2 +/- 8.0 degrees) compared with that of the patients in Groups 1 (80.6 +/- 6.8 degrees, p = 0.02) and 3 (80.1 +/- 6.2 degrees, p = 0.009). However, there was no difference among the groups with respect to the effectiveness of the analgesia, as measured with use of either the visual-analog or the verbal pain-rating scale, or in the prevalence of side effects, including somnolence, urinary retention, nausea and vomiting, or pruritus. Serum concentrations of bupivacaine were well below toxic levels. It was our conclusion that that and intra-articular injection of thirty milliliters of 0.5 percent bupivacaine and 1:200,000 epinephrine in saline solution after closure of the wound decreases the need for narcotics and increases the range of motion after an elective knee replacement. The clinical importance of the amount of increased motion is questionable and needs long-term monitoring.