Post-thoracotomy analgesia and perioperative outcome.

Post-thoracotomy pain is the most severe form of pain after surgery and is continuously exacerbated by ventilatory function. Due to the multiplicity of nociceptive inputs from the chest wall, thoracic viscera, diaphragm and postoperative chest tubes, postoperative pain may be difficult to control with single modalities. The aim is excellent analgesia with function i.e. normal ventilation and rapid mobilisation. A variety of agents and techniques have been shown to be effective analgesics with varying degrees of functional success. These include systemic opioids, NSAIDS and ketamine, regional analgesia (including epidural, spinal, paravetebral, intercostal and intrapleural techniques) and cryoanalgesia. The most popular and probably most effective technique at the present time is thoracic epidural analgesia using a combination of different local anesthetic agents and opioids. There are few data indicating any influence on outcome of different postthoracotomy analgesic techniques. Improvement in outcome requires a co-ordinated approach from all caregivers using the best possible analgesic techniques.

Post-thoracotomy pain control.

Publications on post-thoracotomy pain control obtained by Medline search were reviewed from June 1997 to July 1998. The main focus points in the past year were the effect of new surgical techniques on analgesia after thoracic surgery and the use of extrapleural catheters in the paravertebral space as a method of continuous intercostal nerve block. Epidural and patient-controlled analgesia techniques are still widely used and are mostly effective, but some patients may still have unacceptable levels of pain in the first 24 hours.

Pharmacokinetics of three doses of epidural ropivacaine during hysterectomy and comparison with bupivacaine.

PURPOSE: Ropivacaine is a new long-acting aminoamide local anaesthetic, structurally related to bupivacaine. The clinical efficacy of 125 mg, 187.5 mg and 250 mg ropivacaine have been reported and compared with 125 mg bupivacaine for epidural analgesia during hysterectomy. In the pharmacokinetic part of this study the objectives were to 1) determine the dose proportionality in the pharmacokinetics of epidural ropivacaine, and 2) compare the pharmacokinetics of 125 mg ropivacaine and 125 mg bupivacaine. METHODS: In a randomized, double-blind controlled study, patients received one of four treatment regimens with ropivacaine (125, 187.5 or 250 mg) or bupivacaine (125 mg) as a 25 ml epidural bolus administered over three minutes. Peripheral venous blood samples were collected over 24 hr for ropivacaine or bupivacaine quantification using gas chromatography with nitrogen sensitive detection. Pharmacokinetic variables were derived from plasma concentration-time curve data. RESULTS: Fifty two women entered the study. Demographic characteristics were similar among groups. Six patients were excluded due to inadequate sensory block or an insufficient number of plasma samples. The peak plasma concentration (Cmax) of ropivacaine and the total area under the plasma concentration-time curve (AUC) increased proportionally with the dose. Apparent plasma clearance (CL) and the terminal half-life (t1/2) were similar in the three ropivacaine groups. When compared with the 125 mg ropivacaine group, the bupivacaine group had a longer terminal half life (P < 0.05). CONCLUSIONS: Epidural ropivacaine displays dose-proportional pharmacokinetic behaviour for doses of 125 mg to 250 mg. Ropivacaine has a shorter terminal half-life than bupivacaine.

Intraoperative awareness in fast-track cardiac anesthesia.

BACKGROUND: Fast-track cardiac anesthesia, using low-dose narcotics combined with short-acting anesthetic and sedative agents, facilitates early tracheal extubation after cardiac surgery. The incidence of awareness with this anesthetic technique has not been investigated previously. The purpose of this study was to prospectively investigate the incidence of intraoperative awareness with explicit memory of events during fast-track cardiac anesthesia. METHODS: Data were collected prospectively over a 4-month period from 617 consecutive adult patients undergoing cardiac surgery at a university hospital. All patients received a fast-track cardiac anesthetic regimen. Patients underwent a structured interview by a research nurse 18 h after extubation. A standard set of questions was asked during this interview to determine if the patient had explicit memory of any event from induction of anesthesia to recovery of consciousness. RESULTS: Nine patients did not complete a postoperative interview because of death (n = 7) or postoperative confusion (n = 2). The last memory before surgery reported in 420 (69.1%) patients was waiting in the holding area at the operating suite, and in the remaining 188 (30.9%) patients it was lying on the operating table before induction of anesthesia. Two patients (0.3%) had explicit memory of intraoperative events. One of the two patients also had explicit memory of pain. Neither patient reported adverse psychological sequelae. CONCLUSIONS: The authors report an incidence of awareness in fast-track cardiac anesthesia of 0.3%. This is the lowest incidence of awareness currently reported during cardiac surgery. This low incidence of awareness may be related to the use of a balanced anesthetic technique involving the continuous administration of volatile (isoflurane) or intravenous (propofol) anesthetic agents before, during, and after cardiopulmonary bypass.

Epidural bupivacaine-morphine analgesia versus patient-controlled analgesia following abdominal aortic surgery: analgesic, respiratory, and myocardial effects.

BACKGROUND: The efficacy and effects of epidural analgesia compared with patient-controlled analgesia (PCA) have not been reported in patients undergoing major vascular surgery. We compared the effects of epidural bupivacaine-morphine with those of intravenous PCA morphine after elective infrarenal aortic surgery. METHODS: Forty patients classified as American Society of Anesthesiologists physical status 2 or 3 received general anesthesia plus postoperative PCA using morphine sulfate (group PCA; n = 21) or general anesthesia plus perioperative epidural morphine-bupivacaine (group EPI; n = 19) during a period of 48 h. During operation, EPI patients received 0.05 mg/kg epidural morphine and 5 ml 0.25% bupivacaine followed by an infusion of 0.125% bupivacaine with 0.1% morphine (0.1 mg/ ml); group PCA received 0.1 mg/kg intravenous morphine sulfate. Continuous electrocardiographic monitoring (V4 and V5 leads) was performed from the night before surgery until 48 h afterward. Respiratory inductive plethysmographic data were recorded after tracheal extubation. Visual analog pain scores at rest and after movement were performed every 4 h after extubation. RESULTS: Nurse-administered intravenous morphine and time to tracheal extubation were less in group EPI, as were visual analog pain scores at rest and after movement from 20 to 48 h. Complications and the duration of intensive care unit and hospital stay were comparable. There was a similar, low incidence of postoperative apneas, slow respiratory rates, desaturation, and S-T segment depression. CONCLUSIONS: Epidural morphine-bupivacaine is associated with reduced early postoperative intravenous opioid requirements, more rapid tracheal extubation, and superior analgesia after abdominal aortic surgery, with comparable respiratory effects.

Comparison of lorazepam alone vs lorazepam, morphine, and perphenazine for cardiac premedication.

PURPOSE: To compare the effects of two premedication regimens on cardiorespiratory variables, sedation, and anxiety in patients scheduled for coronary artery bypass graft (CABG) surgery. METHODS: This was a prospective randomized, double-blind clinical trial. Sixty-eight patients were monitored for 1.5 hr before and 2.0 hr after premedication with lorazepam (0.03 mg.kg-1 sl), morphine (0.15 mg.kg-1 im), and perphenazine (0.05 mg.kg-1 im) [Group 1], or with lorazepam (0.03 mg.kg-1 sl) and saline (1.5 ml im) [Group 2]. All were continuously monitored with a 12-lead ECG ST monitors, respiratory inductive plethysmography (RIP), digital pulse oximetry, intra-arterial blood pressure, and arterial blood gas analysis. Sedation and anxiety scores were also recorded. RESULTS: The incidence and duration of myocardial ischaemia was low and similar in Groups 1 and 2. Patients in Group 1, but not in Group 2, had a greater number of events (P < 0.04) and duration (P < 0.02) of O2 desaturation; higher PaCO2 (P < 0.001), and more haemodynamic events (P < 0.006) after premedication when compared with baseline. There was no difference in RIP or ECG variables between the two groups. Following premedication, both groups reported reduced anxiety scores and elevated sedation scores (P < 0.01), with sedation greater in Group 1 than in Group 2 (P < 0.01). CONCLUSION: In CABG patients, premedication with lorazepam provides adequate anxiolysis and sedation, and the addition of morphine and perphenazine results in elevated PaCO2, arterial haemoglobin desaturation, and potentially adverse haemodynamic changes.

Tranexamic acid reduces blood loss, transfusion requirements, and coagulation factor use in primary orthotopic liver transplantation.

BACKGROUND: Patients with end-stage liver disease frequently incur large-volume blood loss during liver transplantation associated with mechanical factors, preexisting coagulopathy, and intraoperative fibrinolysis. METHODS: Between April 1992 and May 1994, the authors of this double-blind, randomized, placebo-controlled study examined the effect of high-dose tranexamic acid (maximum of 20 g) on blood loss and blood product requirements in patients undergoing primary isolated orthotopic liver transplantation. Primary outcome measures were volume of blood loss (intraoperative blood loss and postoperative drainage) and erythrocyte, plasma, platelet, and cryoprecipitate use during surgery and the first 24 h of intensive care unit stay. RESULTS: Patients receiving tranexamic acid (n = 25) had less intraoperative blood loss (median, 4.3 l; interquartile range, 2.5 to 7.9; P = 0.006) compared with the placebo group (n = 20; median, 8 l; interquartile range, 5 to 15.8), and reduced intraoperative plasma, platelet, and cryoprecipitate requirements. Median perioperative erythrocyte use was 9 units (interquantile range, 4 to 14 units) in patients receiving tranexamic acid and 13 units (interquantile range, 7.5 to 31 units) in controls (P = 0.03). Total perioperative donor exposure was 20.5 units (interquantile range, 16 to 41 units) in patients receiving tranexamic acid and 43.5 units (interquantile range, 29.5 to 79 units) in controls (P = 0.003). Results for postoperative wound drainage were similar. Hospital stay and need for retransplantation were comparable in both groups. No patient in either group showed clinical evidence of hepatic artery or portal venous thrombosis within 1 month of transplantation. CONCLUSIONS: High-dose tranexamic acid significantly reduces intraoperative blood loss and perioperative donor exposure in patients with end-stage parenchymal liver disease who are undergoing orthotopic liver transplantation, with marked reductions in platelet and cryoprecipitate requirements.

Cocaine toxicity and isoflurane anesthesia: hemodynamic, myocardial metabolic, and regional blood flow effects in swine.

OBJECTIVES: Increasing numbers of people use cocaine recreationally and may require anesthesia care, having recently abused the drug. However, no data currently exist concerning potential interactions between toxic levels of cocaine and volatile anesthetic agents. This study investigated the effects of cocaine infusion on systemic hemodynamics, myocardial metabolism, and regional organ blood flow in relation to depth of isoflurane anesthesia. DESIGN: Prospective, randomized, controlled trial. SETTING: A laboratory at a university medical center. PARTICIPANTS: Twelve miniature pigs. INTERVENTIONS: An open-chest swine model was used. Isoflurane (ISO) was the sole anesthetic, administered at 0.75 and 1.5 minimum alveolar concentration (MAC), and cocaine was infused (n = 6) at a rate of 0.5 mg/kg/min. Control animals (n = 6) received an equivalent amount of normal saline. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary arterial pressures and thermodilution cardiac output data were collected at 0.75 MAC and 1.5 MAC ISC. Regional myocardial and blood flows to other organs were measured using radiolabeled microspheres. Arrhythmias and altered ventricular conduction were noted only in the cocaine group, along with significant elevations in diastolic arterial pressure, coronary perfusion pressure, and systemic vascular resistance. Increased subendocardial blood flow occurred during cocaine infusion (p = 0.03); subepicardial perfusion was unchanged. Cerebral (p < 0.01) and spinal cord (p < 0.05) blood flows were reduced in animals receiving cocaine. Other organ blood flows were unchanged with depth of anesthesia or cocaine administration, with the exception of splenic blood flow (p < 0.04). CONCLUSIONS: Moderately toxic cocaine levels occurring during isoflurane at 0.75 MAC and 1.5 MAC are associated with hemodynamic abnormalities, a marked increase in systemic vascular resistance, and a tendency to produce cardiac arrhythmias. A reversal of endo/epicardial myocardial perfusion ratio occurs associated with cocaine infusion during ISO anesthesia. This is probably not related to a primary redistribution of subendocardial blood flow and may be related to a combination of increased myocardial oxygen demand and epicardial coronary vasoconstriction. The reductions in cerebral and spinal cord perfusion observed may explain, in part, the neurologic sequelae of cocaine toxicity.

A double-blind comparison of ropivacaine 0.5%, 0.75%, 1.0% and bupivacaine 0.5%, injected epidurally, in patients undergoing abdominal hysterectomy.

PURPOSE: Ropivacaine is a new long-acting, injectable local anaesthetic currently undergoing clinical investigation world wide. It is structurally very similar to bupivacaine, but with less potential for central nervous system or cardiac toxicity. The purpose of this double-blind study was: to investigate the dose-response relationship of increasing doses of ropivacaine on the quality of anaesthesia and the duration of both motor and sensory blockade, and to compare these results with an established local anaesthetic, bupivacaine. METHODS: One hundred and twenty five patients were randomly assigned to one of four treatment groups and 116 completed the study. Epidural anaesthesia was established using 25 ml test solution, injected over three minutes following a satisfactory test dose. Sensory onset, spread and duration, using the pin prick method, and motor scores using a modified Bromage scoring system were compared. RESULTS: A dose/response relationship was observed with increasing doses of ropivacaine for all variables tested except analgesia and muscle relaxation (P < 0.01). There were differences in: (i) motor onset (Levels 1 and 2), when ropivacaine 1.0% was compared with ropivacaine 0.75% and 0.5% (P < 0.05); (ii) in sensory duration at all levels except T6 when ropivacaine was compared with ropivacaine 0.5% (P < 0.05); (iii) differences in sensory duration at T12 and S1 when ropivacaine 1.0% was compared with bupivacaine 0.5% (P < 0.05); (iv) differences in motor duration at all levels when ropivacaine 1.0% was compared with ropivacaine 0.5% (P < 0.05). No serious adverse events were reported in this study. CONCLUSION: Increasing doses of ropivacaine were associated with an increased clinical effect. The most consistent differences occurred when ropivacaine 1.0% was compared with 0.5% and the least consistent between ropivacaine 0.5%, 0.75% and bupivacaine 0.5%. The main difference between ropivacaine 1.0% and bupivacaine was in sensory duration. No serious adverse events were reported.

Acute pain after thoracic surgery predicts long-term post-thoracotomy pain.

OBJECTIVE: Long-term pain is a common sequela of thoracotomy, occurring in approximately 50% of patients 2 years after thoracic surgery. Despite this alarming statistic, little is known about the factors responsible for the transition of acute to chronic pain. The aim of the present study is to identify predictors of long-term post-thoracotomy pain. DESIGN: Follow-up was for 1.5 years for patients who had participated in a prospective, randomized, controlled trial of preemptive, multimodal analgesia. SETTING: Subjects were recruited from a tertiary care center. PATIENTS: Thirty patients who had undergone lateral thoracotomy were followed up by telephone, administered a structured interview, and classified according to long-term pain status. MAIN OUTCOME MEASURES: Present pain status was measured by a verbal rating scale (VAS). Measures obtained within the first 48 h after surgery were compared between patients with and without pain 1.5 years later. These include VAS pain scores at rest and after movement, McGill Pain Questionnaire data, patient-controlled morphine consumption (mg), and pain thresholds to pressure applied to a rib contralateral to the thoracotomy incision. RESULTS: Fifty-two percent of patients reported long-term pain. Early postoperative pain was the only factor that significantly predicted long-term pain. Pain intensity 24 h after surgery, at rest, and after movement was significantly greater among patients who developed long-term pain compared with pain-free patients. A significant predictive relationship was also found at 24 and 48 h using the McGill Pain Questionnaire. Cumulative morphine was comparable for the two groups. Pain thresholds to pressure applied to a rib contralateral to the incision did not differ significantly between the groups. CONCLUSION: Aggressive management of early postoperative pain may reduce the likelihood of long-term post-thoracotomy pain.

A double-blind, placebo-controlled trial of transdermal fentanyl after abdominal hysterectomy. Analgesic, respiratory, and pharmacokinetic effects.

BACKGROUND: A randomized, double-blind, placebo-controlled trial was conducted to assess the analgesic, pharmacokinetic, and clinical respiratory effects of 72-h application of two transdermal fentanyl (TTSF) patch sizes in patients undergoing abdominal hysterectomy. METHODS: TTSF patches releasing 50 micrograms/h (TTSF-50) or 75 micrograms/h (TTSF-75) fentanyl or placebo patches were applied to 120 women 2 h before abdominal hysterectomy under general anesthesia. Postoperatively, all patients had access to supplemental morphine using patient-controlled analgesia pumps. Each patient was attended continuously by a research nurse for 8 h on the night before surgery and for 84 h after patch application. The following data were collected: visual analog scale pain scores, supplementary analgesia, fentanyl plasma concentration (4-h intervals), continuous hemoglobin saturation (pulse oximetry), respiratory pattern (continuous respiratory inductive plethysmography), and adverse effects (nausea, vomiting, pruritus). Data analysis included analysis of variance, Kruskal-Wallis, and chi-squared. P < 0.05 was considered significant. RESULTS: There were no demographic differences among groups. Visual analog scale pain scores were significantly lower for the TTSF-75 group, and supplemental morphine was significantly decreased in the TTSF-75 group in the postanesthesia care unit and for both the TTSF-50 and the TTSF-75 group for 8-48 h postoperatively. Between 5 and 36 h, the TTSF groups had significantly increased abnormal respiratory pattern including apneic episodes (tidal volume of less than 100 ml for more than 15 s) and episodes of slow respiratory rate (less than 8 breaths/min persisting for more than 5 min) and significantly increased requirement for oxygen supplementation. Nine patients in the TTSF groups were withdrawn because of severe respiratory depression compared to none in the placebo group. No significant between-group differences were present in the incidence of nausea, vomiting, or pruritus. Although fentanyl plasma concentration was higher in the TTSF-75 group than in the TTSF-50 group, the differences were not significant. Fentanyl plasma concentration decreased significantly 48 h after patch application. CONCLUSIONS: Application of TTSF patches 2 h preoperatively is associated with moderate supplementary opioid requirements for analgesia in the early postoperative period and ongoing opioid supplementation for at least 72 h. Although good analgesia is the result of this combination therapy, it is associated with a high incidence of respiratory depression requiring intensive monitoring oxygen supplementation, removal of the TTSF patches in approximately 11% of the patients and opioid reversal with naloxone in approximately 8% of the patients.

Oxygenation and ventilation characteristics of thoracic surgical patients the night before surgery.

Studies of the respiratory effects of perioperative analgesic and anesthetic agents are complicated by evidence that healthy subjects and those with COPD may have abnormalities of oxygenation and ventilation during sleep. This report thus characterizes respiration during sleep preoperatively in a population frequently examined in postoperative analgesia studies. Sixty-two thoracic surgical patients were monitored by continuous respiratory inductive plethysmography, 49 of whom also had continuous pulse oximetry and bi-hourly blood gas measurements. The mean respiratory rate (RR) at each hour during sleep was similar to the awake RR (P > 0.06). The minimum RR during sleep was 7.6 +/- 2.1 (2.6-9.8; median 7.9). At least 1 apnea (tidal volume < 100 mL for > or = 15 sec) occurred in 77% of subjects, and 32% had > or = 1 slow respiratory rate (SRR; 5-min RR < 10 beats/min) episode. The mean SpO2 for hours 2 to 4 was significantly less than while awake (P < 0.0015), but the differences were < or = 1.1%. The minimum SpO2 was 88 +/- 7% (62-97; 89) and 40% of subjects had > or = 1 desaturation (DESAT90; SpO2 < 90% for > or = 15 sec) episode. The pH at hours 2 and 4 was significantly (P < 0.0009) less than while awake, but the differences were only 0.02. Other bi-hourly pH, PaCO2, and PaO2 values were similar to the awake values (P > 0.02). Interpatient variability was high, especially for episodic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Multimodal analgesia before thoracic surgery does not reduce postoperative pain.

Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kg-1 i.m. with perphenazine 0.03 mg kg-1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05 mg kg-1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200,000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), PaCO2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain.