Gerhard Brodner

A Multimodal Approach to Control Postoperative Pathophysiology and Rehabilitation in Patients Undergoing Abdominothoracic Esophagectomy

This two-armed study was designed to determine whether recovery after esophageal resection may be improved by introducing a new multimodal approach. For 8 mo after the new approach was introduced, all patients undergoing abdominothoracic esophageal resection were studied (Group 2; n = 42). For comparison, a retrospective analysis was also conducted using the data of all patients who had undergone this operation in the 8 mo before the introduction of the new regimen, when the traditional therapy was still in use (Group 1; n = 49). All patients received an epidural catheter at the level of T6-9 before the induction of general analgesia. Afterward, Group 1 patients were operated under general anesthesia. For postoperative pain relief, a mixture of bupivacaine 1.25 mg/mL and sufentanil 1 micro g/mL was administered during 5 days without titration of the quality of analgesia. Patients in Group 2 received a preoperative bolus of 10-15 mL bupivacaine 2.5 mg/mL and 20-30 micro g sufentanil. After sensory block up to T4 was confirmed, general anesthesia was introduced and intraoperatively combined with a continuous infusion of 5 mL/h of a solution containing bupivacaine 1.75 mg/mL and sufentanil 1 micro g/mL. Postoperatively, the epidural infusion rate was adjusted to the need of the individual patients, who were able to administer themselves additional bolus doses of 2 mL with a lockout time of 20 min. Early tracheal extubation and forced mobilization were pursued to improve recovery. Demographic data of both groups were comparable. The pain relief of Group 2 patients was superior to that of patients in Group 1. The nitrogen balance of a subgroup of nine matched pairs of patients with comparable nutritional status was less negative in Group 2 patients on Postoperative Days 1 and 2. Patients in Group 2 were tracheally extubated earlier (mean 6.7 vs 25.1 h after admission to the intensive care unit [ICU]), mobilized earlier (mean 1.2 vs 2.0 days after surgery), discharged from the ICU earlier (mean 1.7 vs 4.0 days), and fulfilled criteria for discharge from the ICU (mean 1.8 vs 4.1 days) and from the intermediate care unit earlier (4.9 vs 6.4 days). We conclude that the multimodal approach may improve recovery and thus reduce costs after abdominothoracic esophageal resection. Implications: Analgesia and blockade of the perioperative stress response, combined with other aspects of postoperative therapy, may improve recovery after surgery. The intensive care unit stay after esophageal resection was reduced by a new regimen (thoracic epidural analgesia, early tracheal extubation, forced mobilization). This approach may influence the cost of major surgery. (Anesth Analg 1998;86:228-34)

Multimodal perioperative management--combining thoracic epidural analgesia, forced mobilization, and oral nutrition--reduces hormonal and metabolic stress and improves convalescence after major urologic surgery.

We sought in this prospective study to use a multimodal approach to reduce stress and improve recovery in patients undergoing major surgery. During an initial study period, 30 patients were randomly allocated to receive general anesthesia (GA; Group 1) or a combination of GA and intraoperative thoracic epidural analgesia (TEA; Group 2) when undergoing radical cystectomy. Parenteral nutrition was provided for 5 days after surgery. During the second period, 15 patients were treated with a multimodal approach (Group 3) consisting of intraoperative GA and TEA, postoperative patient-controlled TEA, early oral nutrition, and enforced mobilization. Data for plasma and urine catecholamines, plasma cortisol, the nitrogen balance, the postoperative inflammatory nutrition index, pain relief, fatigue, sleep, overnight recovery, recovery of bowel function, and mobilization were recorded up to the fifth postoperative day. Plasma concentrations of catecholamines and cortisol were comparable in all patients, but those in Group 3 had lower levels of urinary catecholamine excretion. Protein intake was more effective with parenteral nutrition. Nitrogen balances were less negative, and the postoperative inflammatory nutrition index score increased significantly in the traditional groups but not in Group 3. Multimodally treated patients reported less fatigue and better overnight recovery. Along with improved pain relief, recovery of bowel function, and ambulation, there were no differences in the postoperative complication rates among the three groups. The multimodal approach reduced stress and improved metabolism and recovery after radical cystectomy.

Epidural analgesia with local anesthetics after abdominal surgery : Earlier motor recovery with 0.2% ropivacaine than 0.175% bupivacaine

UNLABELLED The aim of this prospective, randomized, double-blinded study was to compare pain relief, side effects, and ability to ambulate during epidural anesthesia with ropivacaine 0.2% plus sufentanil versus bupivacaine 0.175% plus sufentanil after major gastrointestinal surgery. Epidural catheters were inserted at T8-11, and 30 microg of sufentanil with 15 mL of ropivacaine 0.75% (Group 1, n = 42) or bupivacaine 0.5% (Group 2, n = 44) was injected. General anesthesia was induced, a continuous epidural infusion (5 mL/h) was then begun with 1 microg/mL sufentanil plus ropivacaine 0.2% (Group 1) or bupivacaine 0.175% (Group 2). Postoperatively, the infusion rate was adjusted to individual requirements. Patients were also able to receive additional 2-mL bolus doses every 20 min. Demographic data (except for gender and height), analgesia, drug dosage, and side-effects, including motor blockade (Bromage score), were similar in both groups, but mobilization recovered more quickly in Group 1. Gender, age, ASA physical status, duration of surgery, and intraoperative blood loss had no effect on mobilization. We conclude that epidural analgesia is effective and safe with both regimens. There is not necessarily a correlation between the Bromage score and the desired outcome of mobilization. The ability to walk postoperatively is hastened if ropivacaine is used instead of bupivacaine. IMPLICATIONS Regarding pain relief and side effects, epidural analgesia with ropivacaine 0.2% and sufentanil 1 microg/mL yields pain scores and pain intensity comparable to those for the well evaluated combination of bupivacaine 0.175% and sufentanil 1 microg/mL. However, earlier recovery of the ability to walk unassisted in patients receiving the combination of ropivacaine and sufentanil may result in their earlier rehabilitation.

The Effects of Adding Sufentanil to Bupivacaine for Postoperative Patient-controlled Epidural Analgesia

We tested the hypothesis that postoperative patient-controlled epidural analgesia was more effective with the combination of sufentanil and bupivacaine (Group 2) than with bupivacaine alone (Group 1). One hundred patients undergoing thoracic, upper abdominal, and aortic surgery were provided with an epidural catheter and randomly allocated to one of the two groups. Postoperatively, patients were monitored in a postanesthetic care unit for at least 1 day before they were transferred to a ward. Both groups had similar demographics and operations. Pain treatment was continued for 4.4 +/- 0.6 and 4.5 +/- 0.7 days for Groups 1 and 2, respectively. Although Group 2 patients needed less volume of the epidural analgesics on Postoperative Days 1 and 2, they reported lower pain intensity at rest and during activity for the first three postoperative days. The groups did not differ from each other regarding the incidence of respiratory depression. There was no late respiratory depression; however, three cases of early respiratory depression were detected and easily treated (Group 1 one event, Group 2 two events). Motor block was only seen in patients with lumbar epidural catheters. There was no difference between groups, and all patients with thoracic catheters could be mobilized beginning on the first postoperative day. We conclude that 1) the addition of sufentanil to a small-dose bupivacaine augments epidural analgesia and 2) thoracic epidural catheters should be used for postoperative analgesia after abdominal or thoracic surgery. (Anesth Analg 1997;85:124-9)

Postoperative analgesia after knee surgery: a comparison of three different concentrations of ropivacaine for continuous femoral nerve blockade.

BACKGROUND: The most effective ropivacaine concentration for femoral infusion after total knee arthroplasty is currently ill defined. We designed the present study to compare ropivacaine in three different concentrations (0.1, 0.2, and 0.3%) to evaluate analgesic quality, when administered as a continuous infusion with frequent infusion adjustments in patients receiving a combined femoral and sciatic nerve block. Secondary aims were to evaluate side effects such as motor blockade, rehabilitation indices, and ropivacaine plasma concentrations. METHODS: One hundred twenty-two patients undergoing total knee arthroplasty under combined general and regional anesthesia received femoral infusions of ropivacaine 0.1, 0.2, or 0.3%. Infusions were started after initial loading doses of 30 mL ropivacaine 0.5% into the femoral catheter and a sciatic catheter and were targeted to dynamic pain scores of 40 mm. Pain and side effects were assessed 1 h after tracheal extubation and on the first, second, third, fourth, and fifth postoperative days. Ropivacaine plasma concentrations were measured 24, 48, and 72 h after the start and 24 h after termination of femoral infusions in patients receiving ropivacaine 0.2% or 0.3%. RESULTS: Ropivacaine 0.1% provided ineffective analgesia. Ropivacaine 0.2% and 0.3% provided equivalent analgesia. Maximum infusion rates were 15.39 and 13.77 mL/h for ropivacaine 0.2% and 0.3%, respectively. There were no significant differences in motor blockade, mobilization, or ropivacaine plasma concentrations, which remained below toxic levels throughout the study period. CONCLUSION: Ropivacaine 0.2% and 0.3% were similar in terms of analgesic quality. Initial infusion rates should be adjusted to 15 mL/h to obtain effective analgesia.

Central and Peripheral Analgesia Mediated by the Acetylcholinesterase-Inhibitor Neostigmine in the Rat Inflamed Knee Joint Model

Intrinsic cholinergic inhibitory pathways present a key modulating system in pain perception.The use of intrathecal (IT) acetylcholinesterase-inhibitors, such as neostigmine, result in analgesia in both preclinical and clinical models. However, whether IT neostigmine suppresses tonic persistent pain or has peripheral sites of antinociceptive action has not been determined. Thus, we studied central (IT) and peripheral (intraarticular; IA) neostigmine in a rat inflamed knee joint model. Inhibition of thermal and mechanical hyperalgesia was assessed over 28 h using a modified Hargreaves box and von Frey hairs, respectively. IT neostigmine resulted in a dose-dependent thermal analgesia (50% of maximal effective dose [ED50] 0-4 h: 6.6 [micro sign]g, 24-28 h: 9.4 [micro sign]g) and mechanical analgesia (ED (50) 0-4 h: 3.5 [micro sign]g, 24-28 h: 4.3 [micro sign]g). IT atropine reversed analgesia by IT neostigmine. IA neostigmine also resulted in an IA atropine reversible dose-dependent increase of thermal analgesia, although it did not exceed 60% of a maximal possible analgesic effect with the largest applied dose (ED50 0-4 h: 76.2 [micro sign]g, 24-28 h: 140.1 [micro sign]g). Partial suppression of mechanical hyperalgesia was observed after IA neostigmine. We conclude that centrally administered neostigmine modulates thermal and mechanical antinociception in this animal model of inflammatory pain. These data suggest a peripheral site of muscarinic antinociception. Implications: This animal study shows that administration of the acetylcholinesteraseinhibitor neostigmine results in enhanced levels of the endogenous neurotransmitter acetylcholine, which seems to act as one of a group of analgesia-modulating compounds at central and peripheral sites in inflammatory pain. (Anesth Analg 1998;86:1027-32)

A multicentre trial comparing different concentrations of ropivacaine plus sufentanil with bupivacaine plus sufentanil for patient-controlled epidural analgesia in labour

Background and objective: To determine the optimal concentration of ropivacaine for bolus-only patient-controlled epidural labour analgesia, three different doses of ropivacaine were evaluated in comparison with bupivacaine in a double-blinded multicentre study. Methods: Four hundred-and-fifty labouring parturients at term in three different academic institutions were randomized to four groups receiving bupivacaine 0.125% with sufentanil 0.75 μg mL−1, ropivacaine 0.125% or 0.175% with sufentanil 0.75 μg mL−1, or ropivacaine 0.2%. After an initial bolus of 10 mL of the study solution, and once visual analogue scores (VAS) were below 30 mm, patient-controlled epidural analgesia was initiated with a bolus of 4 mL, a lockout interval of 15 min and without a background infusion. Variables studied were the quality of analgesia, incidence of side-effects, the degree of motor blockade, and the mode of delivery. Results: Bupivacaine 0.125% and ropivacaine 0.125% with sufentanil proved equally effective in providing labour analgesia without a difference in local anaesthetic consumption (48.6 ± 23 mg bupivacaine vs. 52.1 ± 38 mg ropivacaine), motor blockade or mode of delivery. Ropivacaine 0.175% plus sufentanil enhanced the quality of analgesia of the initial loading dose, whereas ropivacaine 0.2% without sufentanil increased the consumption of local anaesthetics (80.2 ± 34 mg; P < 0.05) and the degree of motor blockade. Conclusion: Despite recent studies indicating that bupivacaine and ropivacaine may not be equipotent, both local anaesthetics provided equi-effective analgesia at equal doses without a difference in side-effects.

Can regional anaesthesia for lymph-node dissection improve the prognosis in malignant melanoma?

BACKGROUND Optimized anaesthetic management might improve the outcome after cancer surgery. A retrospective analysis was performed to assess the association between spinal anaesthesia (SpA) or general anaesthesia (GA) and survival in patients undergoing surgery for malignant melanoma (MM). METHODS Records for 275 patients who required SpA or GA for inguinal lymph-node dissection after primary MM in the lower extremity between 1998 and 2005 were reviewed. The follow-up ended in 2009. Survival was calculated as days from surgery to the date of death or last patient contact. The primary endpoint was mortality during a 10 yr observation period. RESULTS Of 273 patients included, 52 received SpA and 221 GA, either as balanced anaesthesia (sevoflurane/sufentanil, n=118) or as total i.v. anaesthesia (propofol/remifentanil, n=103). The mean follow-up period was 52.2 (sd 35.69) months after operation. Significant effects on cumulative survival were observed for gender, ASA status, tumour size, and type of surgery (P=0.000). After matched-pairs adjustment, no differences in these variables were found between patients with SpA and GA. A trend towards a better cumulative survival rate for patients with SpA was demonstrated [mean survival (months), SpA: 95.9, 95% confidence interval (CI), 81.2-110.5; GA: 70.4, 95% CI, 53.6-87.1; P=0.087]. Further analysis comparing SpA with the subgroup of balanced volatile GA confirmed this trend [mean survival (months), SpA: 95.9, 95% CI, 81.2-110.5; volatile balanced anaesthesia: 68.5, 95% CI, 49.6-87.5, P=0.081]. CONCLUSIONS These data suggest an association between anaesthetic technique and cancer outcome in MM patients after lymph-node dissection. Prospective controlled trials on this topic are warranted.

Early multiple organ failure after recurrent endotoxemia in the presence of vasoconstrictor-masked hypovolemia.

ObjectiveCritically ill patients who develop multiple organ failure during systemic inflammatory states are often predisposed to hypovolemia and vasoconstrictor therapy. Although numerous investigations have evaluated the sequelae of systemic inflammation, no data are available on the contribution of chronic vasoconstrictor-masked hypovolemia to organ dysfunction and morphology. DesignProspective, randomized laboratory investigation. SettingUniversity research laboratory. SubjectsEighteen adult chronically instrumented sheep. InterventionsThe animals were randomly assigned to one of three groups. In the norfenefrine-masked hypovolemia plus endotoxemia (NMH+ENDO) group, mean arterial pressures of 80 mm Hg were maintained by using the &agr;1-adrenergic catecholamine norfenefrine for 52 hrs during hypovolemia. Hypovolemia was induced by hemorrhage (about 23 mL·kg−1) until mean arterial pressures reached 40 mm Hg. Endotoxin (0.5 &mgr;g·kg−1) was then injected after 4, 16, 28, and 40 hrs. The NMH group received norfenefrine-masked hypovolemia but no endotoxin. In the ENDO group, recurrent endotoxemia was induced during normovolemia. Measurements and Main ResultsDespite profound differences in fluid management, cardiovascular filling pressures were not statistically different between groups. Endotoxemia induced norfenefrine-refractory shock (p < .05 vs. the other groups) and contributed to renal dysfunction only during vasoconstrictor-masked hypovolemia. Norfenefrine-masked hypovolemia caused disseminated cardiac cell necrosis independent of endotoxemia (p < .05 vs. ENDO). ConclusionsHypovolemia can be masked when volume status is monitored by filling pressures. In this new model of endotoxemia-associated multiple organ failure, chronic vasoconstrictor-masked hypovolemia turned systemic inflammation into a life-threatening condition with renal and cardiovascular failure. Cardiomyocyte necroses were caused by vasoconstrictor-masked hypovolemia but were unrelated to cardiovascular failure.

Efficacy of intravenous paracetamol compared to dipyrone and parecoxib for postoperative pain management after minor-to-intermediate surgery: a randomised, double-blind trial.

Background and objective Paracetamol has a well established pharmacological profile, but its postoperative efficacy is in question. This double-blind, placebo-controlled study was designed to compare the efficacy of intravenous paracetamol with other intravenous non-opioids as part of a multimodal concept for perioperative pain therapy. Methods Patients undergoing minor-to-intermediate surgery under general anaesthesia were randomly assigned to receive infusions of paracetamol (1 g every 6 h), dipyrone (1 g every 6 h), parecoxib (40 mg every 12 h) separated by infusions of physiological saline 0.9%, or placebo (0.9% saline every 6 h), respectively, for at least 48 h as part of a multimodal pain concept. Patient-controlled piritramide was administered as rescue medication. Dependent variables were recorded 1, 6, 18, 30 and 42 h after extubation and 1 week after surgery. Surgical and associated pain was scored as the primary outcome on a visual analogue scale. Additionally, time to first dose and total piritramide dosage, satisfaction, respiratory depression, nausea, vomiting, sedation, itching and sweating were recorded. Results A total of 196 patients were recruited. The efficacy of paracetamol was similar to that of the other non-opioid analgesics. Surgical pain was reduced with all non-opioids compared to placebo; there was no effect on associated pain. Piritramide dosage and incidence of side effects were not reduced. Conclusion Intravenous paracetamol has equivalent efficacy to non-opioids dipyrone and parecoxib that improves postoperative pain therapy when used as part of a multimodal concept after minor-to-intermediate surgery.