Hartmut Buerkle

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.

Postoperative Analgesia by Intra-articular Neostigmine in Patients Undergoing Knee Arthroscopy

Background Recently, the spinal administration of neostigmine was shown to produce a dose‐dependent analgesia. However, this analgesia is limited by adverse effects. The purpose of this study was to examine the analgesic action of peripheral muscarinic receptors by administering intra‐articular neostigmine after operation in patients undergoing knee arthroscopy. Methods Sixty patients (classified as American Society of Anesthesiologists status I or II) having arthroscopic meniscus repair during general anesthesia were randomized to receive, in a double‐blind manner, after operation 125, 250, or 500 micro gram intra‐articular neostigmine; 2 mg intra‐articular morphine; or as control groups intra‐articular saline or 500 micro gram neostigmine given subcutaneously (SC). Visual analog pain scores (VAS), duration of analgesia as defined by first demand for patient‐controlled analgesia by morphine, and subsequent 48‐h consumption of morphine were evaluated. Results Intra‐articular (500 micro gram) neostigmine resulted in significant VAS reduction 1 h after injection compared with patients given intra‐articular saline and with those given intra‐articular morphine. Analgesia lasted longer after 500 micro gram intra‐articular neostigmine (350 +/‐ 126 min) compared with intra‐articular morphine (196 +/‐ 138 min; P < 0.05) or with the control groups (intra‐articular saline, 51 +/‐ 11 min; SC neostigmine, 46 +/‐ 8 min; P < 0.05). The need for supplementary analgesia was significantly higher in control groups than for patients given intra‐articular morphine or 500 micro gram intra‐articular neostigmine. No significant analgesic effects were observed for the two lower doses of intra‐articular neostigmine. Among all study groups, no adverse effects were observed. Conclusions Intra‐articular injection of the acetylcholinesterase inhibitor neostigmine produced a moderate but significant analgesic effect. Several mechanisms such as the hyperpolarization of neurons, reduction in the release of pronociceptive neurotransmitters, or activation of the nitric oxide‐cyclic guanosine monophosphate pathway might mediate this peripheral cholinergic antinociception by elevating endogenous acetylcholine.

Nociceptive and antinociceptive responses to intrathecally administered nicotinic agonists

Activation of spinal nicotinic receptors evokes a prominent algogenic response. Recently, epibatidine, a potent nicotinic agonist, was found to display an antinociceptive response after systemic administration. To examine the spinal component of this action, effects of three nicotinic agonists epibatidine, cytisine and nicotine--were given intrathecally (IT) and their antinociceptive activity was subsequently assessed. All agents elicited dose-dependent algogenic activity, characterized at lower doses by touch-evoked hyperactivity and at higher doses by intermittent vocalization and marked behavioral activity, with the rank order of potency being epibatidine > cytisine > nicotine. In addition, intrathecal epibatidine elicited a short-lasting, dose-dependent thermal antinociception. In contrast, the other nicotinic agonists at the highest usable dose failed to produce a significant antinociception. Mecamylamine, a nicotinic channel blocker, completely abolished the antinociceptive and algogenic responses of epibatidine. The competitive antagonist, alpha-lobeline, blocked both the analgesic and algogenic responses, but methyllycaconitine inhibited only the algogenic effects of epibatidine. Dihydro-beta-erythroidine, also a competitive antagonist, had no effect on the initial intense algogenic responses. The analgesic response to epibatidine was neither inhibited by naloxone nor by atropine. 2-Amino-5-phosphopentanoic acid, a competitive N-methyl-D-aspartate receptor antagonist, did not affect the analgesic response to intrathecal epibatidine or the intense initial algogenic response. Upon repeated administration (30-min interval), epibatidine (1 microg, IT) exhibited marked and rapid desensitization to both the analgesic and algogenic responses which recovered within 8 h. Pretreatment with two consecutive doses of cytisine (5 microg, IT, 30-min apart) inhibited the agitation and analgesic actions of intrathecal epibatidine. Thus, we contend that in addition to the typical nociceptive response elicited by spinal nicotinic agonists, intrathecal epibatidine also exhibits a pronounced but short-lasting antinociception. The analgesic and algogenic responses to intrathecal epibatidine may be mediated by distinct subtypes of spinal nicotinic receptors as suggested by the antagonist studies.

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.

Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery.

We conducted this double-blinded, randomized study to assess the analgesic effect of repeated administrations of paracetamol, administered as propacetamol, an injectable prodrug formulation of paracetamol, and to compare this with the analgesic effects of morphine. Patients experiencing moderate to severe pain after elective surgical removal of bone-impacted third-molar teeth under general anesthesia were randomly assigned to receive IV propacetamol 2 g (n = 31), IM morphine 10 mg (n = 30), or placebo (n = 34). Five hours later, the treatments were readministered at half of the previous dosages. Standard measures of analgesia were collected repeatedly for 10 h. Propacetamol and morphine were significantly more effective than placebo in all primary measures of analgesia over 5 h after the first administration and globally over 10 h (first and second administrations). After the first dose, 21 of the 34 patients in the placebo group required rescue medication, compared with 6 of the 31 in the propacetamol group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No statistically or clinically significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia. No serious adverse events were reported; adverse events were significantly less frequent in the propacetamol group than in the morphine group (P < 0.027). Propacetamol administered IV in repeated doses (2 g followed by 1 g) has a significant analgesic effect that is indistinguishable from that of morphine administered IM (10 mg followed by 5 mg) after dental surgery, with better tolerability.

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.

Assessment of depth of anesthesia and postoperative respiratory recovery after remifentanil- versus alfentanil-based total intravenous anesthesia in patients undergoing ear-nose-throat surgery.

BackgroundThe authors investigated whether total intravenous anesthesia (TIVA) with precalculated equipotent infusion schemes for remifentanil and alfentanil would ensure appropriate analgesia and that remifentanil would result in better recovery characteristics. MethodsForty consenting patients (classified as American Society of Anesthesiologists physical status I–III) scheduled for microlaryngoscopy were randomized to receive, in a double-blind manner, either remifentanil (loading dose 1 &mgr;g/kg; maintenance infusion, 0.25 &mgr;g · kg−1 · min−1) or alfentanil (loading dose, 50 &mgr;g/kg; maintenance infusion, 1 &mgr;g · kg−1 · min−1) as the analgesic component of TIVA. They were combined with propofol (loading dose, 2 mg/kg; maintenance infusion, 100 &mgr;g · kg−1 · min−1). To insure an equal state of anesthesia, the opioids were titrated to maintain heart rate and mean arterial pressure within 20% of baseline, and propofol was titrated to keep the bispectral index (BIS) less than 60. Neuromuscular blockade was achieved with succinylcholine. Drug dosages and the times from cessation of anesthesia to extubation, verbal response, recovery of ventilation, and neuropsychological testing, orientation, and discharge readiness were recorded. ResultsDemographics, duration of surgery, and anesthesia were similar between the two groups. Both groups received similar propofol doses. There were no difference in BIS values preoperatively (mean, 96), intraoperatively (mean, 55), and postoperatively (mean, 96). Recovery of BIS and times for verbal response did not differ. At 20, 30, and 40 min after terminating the opioid infusion, the peripheral oxygen saturation and respiratory rate were significantly higher in the remifentanil group compared with the alfentanil group. ConclusionsWhen both the hypnotic and analgesic components of a TIVA-based anesthetic are administered in equipotent doses, remifentanil provides a more rapid respiratory recovery, even after brief surgical procedures, compared with alfentanil.

Comparison of the Spinal Actions of the micro-Opioid Remifentanil with Alfentanil and Morphine in the Rat

Background micro‐Opioids administered spinally produce a potent, dose‐dependent analgesic response in preclinical and clinical investigations. Side‐effect profile of these compounds may be altered as a function of pharmacokinetics. The effects of intrathecal and intraperitoneal remifentanil, an esterase‐metabolized micro opioid, alfentanil, and morphine were compared. Methods Intrathecal and intraperitoneal remifentanil, alfentanil, and morphine were examined in rats tested for hind‐paw thermal withdrawal latency. The antinociceptive response was assessed and in parallel a scoring of four different parameters summarized as a supraspinal index to assess supraspinal side‐effect profiles after the several drugs were delivered by the different routes. Results All opioids produced a dose‐dependent analgesic response after intrathecal administration. The ordering of potency (intrathecal ED sub 50 in micro gram) was remifentanil (0.7) > morphine (12.0) > alfentanil (16.3) > GR90291, principal remifentanil metabolite (> 810 micro gram). Time until onset of analgesia after intrathecal or intraperitoneal delivery was morphine > remifentanil = alfentanil. When matched for analgesic effect, the relative duration of action was morphine >> alfentanil > remifentanil. The supraspinal index showed a dose‐dependent increase for all agents. All intraperitoneal drugs showed dose‐dependent increases in antinociception with potency (intraperitoneal ED50 in micro gram) of remifentanil (4.3) > alfentanil (24.4) > morphine (262). Calculation of intrathecal or intraperitoneal ratios for supraspinal side effects/analgesia (supraspinal index ED50 /analgesia ED50) revealed remifentanil to be greatest when intrathecally administered: remifentanil (4 intrathecal: 1.4 intraperitoneal); alfentanil (0.7 intrathecal: 1.5 intraperitoneal); and morphine (1 intrathecal: 5.6 intraperitoneal). Conclusions These observations indicate that remifentanil has a powerful spinal opioid action. Consistent with its lipid‐solubility, it has an early onset like alfentanil but displays a shorter duration of action after bolus delivery. Despite lipid solubility, remifentanil has a significant spinal therapeutic ratio. These observations likely reflect the rapid inactivation of systemically redistributed agent by plasma esterases.

The volatile anesthetic isoflurane prevents ventilator-induced lung injury via phosphoinositide 3-kinase/Akt signaling in mice.

BACKGROUND: Mechanical ventilation leads to ventilator-induced lung injury in animals, and can contribute to acute lung injury/acute respiratory distress syndrome in humans. Acute lung injury/acute respiratory distress syndrome currently causes an unacceptably high rate of morbidity and mortality among critically ill patients. Volatile anesthetics have been shown to exert anti-inflammatory and organ-protective effects in vivo. We investigated the effects of the volatile anesthetic isoflurane on lung injury during mechanical ventilation. METHODS: C57BL/6N mice were ventilated with a tidal volume of 12 mL/kg body weight for 6 hours in the absence or presence of isoflurane, and, in a second series, with or without the specific phosphoinositide 3-kinase/Akt inhibitor LY294002. Lung injury was determined by comparative histology, and by the isolation of bronchoalveolar lavage for differential cell counting and analysis of cytokine levels using enzyme-linked immunosorbent assays. Lung homogenates were analyzed for protein expression by Western blotting. RESULTS: Mechanical ventilation caused increases in alveolar wall thickening, cellular infiltration, and an elevated ventilator-induced lung injury score. Neutrophil influx and cytokine (i.e., interleukin-1&bgr;, and macrophage inflammatory protein-2) release were enhanced in the bronchoalveolar lavage of ventilated mice. The expression levels of the stress proteins hemeoxygenase-1 and heat shock protein-70 were elevated in lung tissue homogenates. Isoflurane ventilation significantly reduced lung damage, inflammation, and stress protein expression. In contrast, phosphorylation of Akt protein was substantially increased during mechanical ventilation with isoflurane. Inhibition of phosphoinositide 3-kinase/Akt signaling before mechanical ventilation completely reversed the lung-protective effects of isoflurane treatment in vivo. CONCLUSIONS: Inhalation of isoflurane during mechanical ventilation protects against lung injury by preventing proinflammatory responses. This protection is mediated via phosphoinositide 3-kinase/Akt signaling.