Satisfaction with epidural and intravenous patient-controlled analgesia.

OBJECTIVE: Postoperative intravenous (i.v.) versus epidural morphine patient-controlled analgesia (PCA) were compared regarding maintenance of initial PCA route, pain levels, side effects, and levels of satisfaction. Additionally, the role of preoperative attitudinal expectations in predicting postoperative levels of satisfaction with pain management as well as maintenance of initial PCA route was evaluated. DESIGN: After either abdominal or thoracic surgery, 70 eligible patients were randomized to receive morphine either through an epidural route (n = 37) or an intravenous PCA pump (n = 33). SETTING: A large tertiary university teaching hospital in a major northeastern city. OUTCOME MEASURES: Patients completed visual analogue rating scales 1 week before surgery regarding attitudes such as expectations of satisfaction with pain management after surgery and expectations of medication efficacy postsurgically. Postoperatively, beginning the day after surgery, patients were asked to complete visual analogue rating scales every 12 hours until they were discharged, for a maximum of 3 postoperative days. The scales evaluated included pain, ability to think, and satisfaction with pain control. RESULTS: There were no significant between-group differences on the postoperative visual analogue scales. Although the overall rate of changing the initial PCA route to which the patients were randomized was identical for both groups (30%), those patients who had thoracic surgery changed their route of PCA administration significantly less when their initial PCA route was epidural (20%) than when their initial PCA route was i.v. (46%) (P <.05). Patients who were satisfied with pain control postoperatively were more likely to have been started on i.v. PCA (P =.001), have lower preoperative expectations of postoperative satisfaction with pain (P <.001), and have higher preoperative expectations of medication effects on postoperative pain (P <.001). Additionally, older patients (P =.007) and patients with lower preoperative expectations of postoperative satisfaction with pain (P =.003) were more likely to adhere to their initial treatment protocol. CONCLUSIONS: Both techniques, i.v. and epidural PCA, result in high levels of satisfaction. Satisfaction with PCA can be accurately predicted in nearly three of four patients based on initial PCA route and preoperative attitudes. Additionally, maintaining the initial treatment plan can be accurately predicted based on age and preoperative attitudes. Patient expectations about pain relief should be addressed preoperatively, particularly with younger patients, for optimal results.

The recovery of cognitive function after remifentanil-nitrous oxide anesthesia is faster than after an isoflurane-nitrous oxide-fentanyl combination in elderly patients.

UNLABELLED: We tested the hypothesis that remifentanil-nitrous oxide (N(2)O) anesthesia shortens postoperative emergence and recovery compared with an isoflurane-N(2)O-fentanyl combination in elderly patients undergoing spinal surgery. A total of 60 patients (>65 yr old) were randomly assigned to one of two groups for maintenance of anesthesia. After the induction with 3.6 +/- 1.2 mg/kg IV thiopental and endotracheal intubation facilitated with 1.4 +/- 0.5 mg/kg succinylcholine, patients were maintained with either 0.5%-1.5% isoflurane, 70% N(2)O, and up to 7 microg/kg fentanyl (iso/fent group) or 48 +/- 11 microg/kg remifentanil and 70% N(2)O (remi group). A mini-mental status examination was used to assess cognitive ability preoperatively, at 15, 30, and 60 min after arrival at the postanesthesia care unit and again 12-24 h postoperatively. The time from the conclusion of anesthesia to spontaneous respiration was similar in both groups. Times to eye opening (4.8 +/- 2.6 vs 2.3 +/- 1.1 min), extubation (6.8 +/- 3.8 vs 3.2 +/- 2.1 min), and verbalization (9.9 +/- 6.2 vs 3.9 +/- 2.6 min) were significantly shorter for the remi group (P < 0.05). Postoperative mini-mental status examination scores were significantly lower in the iso/fent group at 15 (16.3 +/- 5.8 vs 23. 7 +/- 3.3), 30 (20.2 +/- 5.2 vs 26.3 +/- 2.7), and 60 min (23.5 +/- 4.4 vs 27.5 +/- 2.0) (P < 0.001); however, the scores equalized after 12 h. Requirements for postoperative analgesics were similar in the two groups. More patients in the remi group were treated with antiemetics (21 vs 7, P = 0.06). Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit; a stay is often related to multiple administrative issues, rather than cognitive recovery. IMPLICATIONS: Maintenance of anesthesia with remifentanil-nitrous oxide (N(2)O), compared with isoflurane-N(2)O-fentanyl, can safely shorten postoperative recovery of cognitive function in a geriatric population. Earlier recovery may facilitate postoperative neurological assessment. Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit, a stay often related to multiple administrative issues, rather than cognitive recovery.

Acute ethanol treatment modulates delta opioid receptors in N18TG2 cells.

BACKGROUND: The in vitro adaptive responses of delta opiate receptors (DOR) to chronic ethanol treatment have been well documented. The acute effects of ethanol on these receptors are not well characterized beyond its effect on ligand binding. The aim of this study was to evaluate the acute effects of clinically relevant concentrations of ethanol (50-200 mm) on the saturation binding kinetics, receptor/ligand internalization, and agonist stimulation of G-protein coupling in N18TG2 cells expressing the Flag epitope-tagged mouse DOR. METHODS: Confocal microscopy was used to localize Flag epitope-tagged DOR in N18TG2 cells. Saturation binding assays at 4 degrees C and 37 degrees C were conducted in the absence or presence of ethanol on cells not pretreated or pretreated with ethanol for 30 min at 37 degrees C. Highly specific delta agonist, DPDPE ([D-Pen2,D-Pen5]enkephalin), was used in these studies. The effect of ethanol on agonist stimulation of G-protein coupling was examined using [35S]GTPgammaS (guanosine-5'-O-(3-thio)triphosphate) binding to membranes. Agonist-mediated receptor internalization was examined using flow cytometry of cells labeled with the antiserum directed against the Flag epitope, and the ligand internalization was examined using [3H]DPDPE. RESULTS: Ethanol decreased the binding of the agonist [3H]DPDPE, and not the antagonist [3H]diprenorphine, in a dose-dependent manner. These effects were temperature-dependent. Ethanol reversibly inhibited agonist stimulation of [35S]GTPgammaS binding. In non-pretreated cells, ethanol decreased the rate of receptor/ligand internalization, but this effect was not seen in ethanol pretreated cells. Taken together, these results suggest that pretreatment of N18TG2 cells with ethanol induces compensatory mechanisms that allow the receptor to function efficiently in its presence. CONCLUSION: Acute ethanol decreased the binding, agonist-mediated functional coupling and receptor/ligand internalization in N18TG2 cells expressing epitope-tagged DOR. In these cells, 30-min pretreatment with ethanol was sufficient to reverse these effects.

Hyper- and hypoventilation affects spinal motor neuron excitability during isoflurane anesthesia.

UNLABELLED: Increasing evidence indicates that the spinal cord is an important site of anesthetic action necessary for surgical immobility. Whether clinical hyper- or hypoventilation affects motor neuron excitability during general anesthesia is unknown. To clarify this issue, we studied seven adult ASA physical status I or II patients undergoing elective surgery. Spinal motor neuron excitability was determined by measuring the posterior tibial nerve H reflex and F wave. The baseline H reflex and F wave were recorded before anesthesia using electrodes placed over the soleus and abductor hallucis muscles. After inhaled induction, the end-tidal isoflurane concentration in O2 was maintained at 0.8%. Ventilation was controlled to maintain a steady-state ETCO2 of 25 +/- 1 and 45 +/- 1 mm Hg randomly for 20 min. Then the H-reflex and F wave were recorded. The difference in H reflex and F wave were analyzed using Student's paired t-test. The baseline H-reflex amplitude (6.8 +/- 2.7 mV) decreased to 4.0 +/- 2.0 mV (P < 0.01) at an ETCO2 of 25 mm Hg and to 2.0 +/- 2.2 mV (P < 0.01) at an ETCO2 of 45 mm Hg. The F-wave persistence (100%) decreased to 77% +/- 24% (P < 0.05) at an ETCO2 of 25 mm Hg and to 61% +/- 19% at an ETCO2 of 45 mm Hg (P < 0.01). Changing ETCO2 values affected H-reflex amplitude and F-wave persistence (P < 0.05), which suggests a change of spinal cord motor neuron excitability, which may affect surgical immobility. IMPLICATIONS: The spinal cord is important for preventing patient movement during surgery. The likelihood of movement may be predicted by measuring the spinal motor neuron excitability by using the H reflex and F wave. Our results show that intraoperative hyper- and hypoventilation can change the H reflex and F wave, which may affect the probability of patient movement during surgery.

Suppression of spinal cord motoneuron excitability correlates with surgical immobility during isoflurane anesthesia.

BACKGROUND: Recent evidence suggests that the spinal cord is an important site of anesthetic action that produces surgical immobility. Inhalation anesthetics depress the Hoffmann's reflex (H reflex) and F wave, indicating spinal motoneuron suppression. The aim of this study was to assess the correlation between isoflurane-induced immobility and H- and F-wave suppression. METHODS: The baseline H reflex and F wave were measured before anesthesia in 15 adult patients. After induction, 1% end-tidal isoflurane was maintained for 20 min before the H and F waves were reelicited. Using an electric stimulus applied to the forearm and grading the response as movement or no movement, the authors increased or decreased the isoflurane concentration in 0.1% steps, depending on the movement responses. The H and F waves were recorded 20 min after each change of isoflurane concentration. The correlation between H- and F-wave suppression and surgical immobility was analyzed using a paired t test with Bonferroni correction. RESULTS: H-reflex amplitude (2.74 +/- 1.63 mV) and F-wave persistence (70.69 +/- 26.19%) at the highest isoflurane concentration that allowed movement response to a stimulus are different (P < 0.01) from these (1.97 +/- 1.46 mV; 43.16 +/- 22.91%) at the lowest isoflurane concentration that suppressed response. At 0.8% isoflurane, the H-reflex amplitude was 3.69 +/- 1.83 mV with movement and 1.01 +/- 1.14 mV without movement (P < 0.01); F-wave amplitude was 0.29 +/- 0.15 mV with movement and 0.11 +/- 0.06 mV without movement (P < 0.01); F-wave persistence was 80 +/- 22.36% with movement and 34.9 +/- 25.75% without movement (P < 0.01). CONCLUSIONS: The degree of H- and F-wave amplitude and F-wave persistence suppression correlates with movement response, suggesting that isoflurane-suppressive action in the spinal cord plays a significant role in producing surgical immobility.

Computer simulation of cerebrovascular circulation: assessment of intracranial hemodynamics during induction of anesthesia.

OBJECTIVE: The purpose of this project was to develop a computer model of cerebrovascular hemodynamics interacting with a pharmacokinetic drug model to examine the effects of various stimuli on cerebral blood flow and intracranial pressure during anesthesia. METHODS: The mathematical model of intracranial hemodynamics is a seven-compartment, constant-volume system. A series of resistance relate blood and cerebrospinal fluid fluxes to pressure gradients between compartments. Arterial, venous, and tissue compliance are also included. Autoregulation is modeled by transmural pressure-dependent, arterial-arteriolar resistance. The effect of a drug (thiopental) on cerebrovascular circulation was simulated by a variable arteriolar-capillary resistance. Thiopental concentration was predicted by a three-compartment, pharmacokinetic model. The effect site compartment was included to account for a disequilibrium between drug plasma and biophase concentrations. The model was validated by comparing simulation results with available experimental observations. The simulation program is written in VisSim dynamic simulation language for an IBM-compatible PC. RESULTS: The model developed was used to calculate the cerebral blood flow and intracranial pressure changes that occur during the induction phase of general anesthesia. Responses to laryngoscopy and intubation were predicted for simulated patients with elevated intracranial pressure and non-autoregulated cerebral circulation. Simulation shows that the induction dose of thiopental reduces intracranial pressure up to 15%. The duration of this effect is limited to less than 3 minutes by rapid redistribution of thiopental and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension, exceeding the initial intracranial pressure. Further simulation predicts that this untoward effect can be minimized by an additional dose of thiopental administered immediately prior to intubation. CONCLUSION: The presented simulation allows comparison of various drug administration schedules to control intracranial pressure and preserve cerebral blood flow during induction of anesthesia. The model developed can be extended to analyze more complex intraoperative events by adding new submodels.

Spinal anesthesia by local anesthetics stimulates the enzyme protein kinase C and induces the expression of an immediate early oncogene, c-Fos.

To understand the biochemical mechanisms involved in spinal anesthesia, we measured protein kinase C (PKC) activity and expression of immediate early oncogene protein, c-Fos, in the spinal cord. Spinal anesthesia was induced in mice using intrathecal injection of either 10 microL procaine or tetracaine (0.067 M/approximately 2%). Control groups were treated with either saline or ethanol. Animals were killed at 1, 5, and 15 min after the injection and the caudal 3 cm of the spinal cord was processed for biochemical analysis. PKC activity was measured by the transfer of a phosphate group from [gamma-32P]adenosine 5'-triphosphate to the threonine group on a synthetic peptide specific for PKC. Western blot analysis was used to detect changes in c-Fos protein expression. When compared to saline-treated controls, PKC activity was increased significantly (P < 0.0005) in procaine- and tetracaine-treated groups whereas ethanol decreased PKC activity. The less lipid-soluble procaine produced a larger increase in PKC activity than did the more lipid-soluble tetracaine. Moreover, parallel to the effect on PKC activity, procaine was more potent than tetracaine as a c-Fos inducer. These results implicate some role for a PKC- and c-Fos-dependent pathway in the mechanism of spinal anesthesia. However, these results also demonstrate a lack of correlation between an increase in PKC levels and either potency or lipid solubility of the anesthetics. The increased PKC activity may not be the sole mechanism for spinal anesthesia. These data on the effects of local anesthetics on PKC activity and c-Fos in vivo are of relevance for studies aimed at delineating the biochemical basis of spinal and epidural anesthesia.

The antinociceptive effect of S-(+)-ibuprofen in rabbits: epidural versus intravenous administration.

This study was designed to determine whether systemic absorption plays any role in the antinociceptive effect of epidural (EP) sodium S(+)-ibuprofen (IB). One week after surgical implantation of EP catheters, six rabbits were given EP injections with either normal saline (NS) 0.4 mL or IB 10 mg in 0.4 mL NS (Group 1) on separate days. Each animal was injected with IB 10 mg intravenously (i.v.) on another day. Six control rabbits (Group 2) had neither surgery nor any injection. Analgesic testing was performed using electric stimulation through two electrocardiogram (ECG) skin electrodes with built-in adhesive, attached to shaved hip areas using 50 V, 1 Hz, 3 ms, before and 0.5,1,2 and 3 h after injection in Group 1, and in similar times in controls. The 95% confidence intervals (CI) of the mean difference between baseline and maximal nociceptive response latency of all groups were compared using analysis of covariance (ANCOVA) adjusted for baseline measurements. This comparison covered all possible pairs among all groups. Significant antinociceptive effects were seen after EP IB but not after control or i.v. IB. Neither motor dysfunction nor evidence of systemic toxicity or neurotoxicity was observed in any animal.

Effect of cocaine on macromolecular syntheses and cell proliferation in cultured glial cells.

In the present study the effect of cocaine on thymidine, uridine and leucine incorporation was assessed in primary cortical glial and C6 glioma cells. Cocaine exposure for 24 h inhibited thymidine and uridine incorporation in cortical glial and C6 glioma cells. However, the effect of cocaine on uridine incorporation was less prominent compared to thymidine incorporation. High concentrations of cocaine inhibited leucine incorporation in C6 glioma cells but not in cortical glia. Cocaine exposure for four days decreased cell proliferation of cortical glial and C6 glioma cells. Cocaine-induced attenuation of macromolecular syntheses was not due to cell death since cocaine-treated cells were not stained with Trypan Blue and did not release lactate dehydrogenase into culture supernatants. Furthermore, cocaine had no effect on glutamate uptake either in cortical glia or in C6 glioma cells. These results indicate that cocaine inhibits macromolecular syntheses in glial cells. The inhibition of macromolecular syntheses in glial cells may be the mechanism involved in cocaine-induced fetal brain growth retardation.

Electrocardiographic changes during cesarean section: a cause for concern?

A Holter monitor was used to record ST segment changes during cesarean section in 170 consecutive healthy parturients starting 2 h before and ending 3 h after surgery. Lumbar epidural anesthesia (LEA, n = 120) or subarachnoid anesthesia (SA, n = 50) was used. Transthoracic 2-D echocardiograms were obtained in 30 patients from the LEA group. ST depression or elevation occurred 160 times in 44 patients from both groups. Ninety-eight percent of these changes occurred between induction of anesthesia and the end of surgery, with 78% of the episodes registering -1 mV. In the LEA group, the number of episodes tended to increase after delivery, but in the SA group, the frequency remained constant. ST segment depression was recorded in 38% and 14% of patients in the LEA and SA groups, respectively (P < 0.05, x2 analysis). No wall motion abnormality was noted in the echocardiogram during ST segment depression. Neither the 12-lead electrocardiogram nor plasma myocardial specific creatine kinase suggested myocardial damage. The operative events, alone or in combination, including hypertension, tachycardia, hypotension, bradycardia, air embolism (precordial Doppler) were neither specific nor sensitive as predictors of ST segment change (stepwise logistic regression). Tachycardia was associated with ST segment changes in 10% of time epochs (5 min) (P = 0.05, x2 analysis). Thus, ST segment changes during cesarean section are not caused by myocardial ischemia and are not of any clinical consequence.

Intraoperative monitoring of the dorsal sacral roots: minimizing the risk of iatrogenic micturition disorders.

In 31 children (age, 2-17 years) and 1 adult, individual dorsal root action potentials (DRAPs) from the S1-S3 roots were recorded intraoperatively after electrical stimulation of the dorsal penile or clitoral nerves, in preparation for surgery within the cauda equina. In most patients, pudendal afferent activity was present in S2 and S3 bilaterally; in some, the afferent activity was confined to a single root bilaterally, and in one, to a single root on one side. Dorsal root action potentials of small amplitude were recorded from S1 in 15 patients, although in no patient was S1 the primary carrier of these afferents. No lesion of the roots or rootlets carrying significant afferent activity was created during the rhizotomy, and no dysfunction in micturition resulted. We propose that the neurophysiological identification of roots and rootlets carrying afferent activity from the penile or clitoral nerves allows for rhizotomy of the S2 roots with the least possible risk of postoperative micturition and sexual dysfunction.

Lumbar subarachnoid catheterization in rats.

An animal model was developed for the study of subarachnoid (spinal) anesthesia and analgesia under unanesthetized, unsedated and unrestrained conditions. Sprague-Dawley rats were anesthetized with intraperitoneal ketamine (75-100 mg.kg-1). A PE10 catheter was inserted under direct vision into the lumbar subarachnoid space, through partial laminectomy of L1 or L2 with or without removal of adjacent intervertebral ligament. One week after surgery, correct position of the catheter was verified by subarachnoid injection of 0.03-0.05 ml of 1.5% lidocaine, which produced temporary hind limb paralysis in all but one animal in 28 consecutive operations. There was neither mortality nor major complication, intraoperatively or postoperatively. Only 2 animals developed minor subcutaneous would infections which responded to incision, drainage and debridement.

Anesthetic care of a patient with an intracranial hemorrhage after thrombolytic therapy.

Thrombolytic therapy is being used with increasing frequency to treat acute myocardial infarction (MI). It is important for both the general and cardiac anesthesiologist to understand the effects of thrombolysis on hemostasis and myocardial function, since these patients can present for emergent surgery in the cardiac or general operating theater. The authors report a case of a patient who developed an intracranial hemorrhage following thrombolytic therapy that required emergency surgical intervention.

The effects of local anesthetics on maternal and neonatal platelet function.

The effects of bupivacaine (B), lidocaine (L) and 2-chloroprocaine (C) on maternal (M) and neonatal (N) platelet function were studied using in vitro beta-thromboglobulin (beta-tg) release (radioimmunoassay), and in vitro platelet aggregation. Aggregation produced by adenosine diphosphate (ADP), epinephrine and collagen was measured in the presence of 1, 10, 100, 500 or 1000 micrograms/ml concentrations of B, L or C. In addition, spontaneous in vivo beta-tg release was measured in M and N blood. In vivo beta-tg level in M and N blood was approximately double that in non-pregnant subjects (p less than 0.025). In vitro beta-tg release in M and N samples was inhibited only at concentrations exceeding 1000 micrograms/ml, and the inhibition was less in M and N samples than in non-pregnant subjects. None of the anesthetics inhibited aggregation of M or N platelets at 1 and 10 micrograms/ml. Only concentrations of 500 micrograms/ml or greater consistently inhibited platelet aggregation produced by the three aggregants in M and N samples, and L was the least effective of the three agents. Neonatal platelet aggregation was affected more by local anesthetics than was maternal aggregation. It is concluded that plasma local anesthetic concentrations achieved during normal maternal epidural anesthesia do not affect M or N platelet aggregation or beta-tg release.

Sufentanil pharmacokinetics in neurosurgical patients.

The effects of respiratory alkalosis and dehydration on the pharmacokinetics of sufentanil have been determined. Forty neurosurgical patients entered the study: group I (n = 20) had spinal surgery while group II (n = 20) had elective craniotomies. All patients received a single intravenous bolus of sufentanil (2 micrograms/kg) during induction of anesthesia. Patients in group II received furosemide (40 mg) and mannitol (1 g/kg) prior to surgery and were hyperventilated to a PaCO2 below 30 mmHg. The anesthetic management was identical in both groups. Arterial blood samples were collected to determine sufentanil concentrations (RIA), blood gases, pH, hematocrit and electrolytes. Patients in group II had significantly higher blood pH and urinary output when compared to group I (p less than 0.05). Plasma sufentanil concentrations were best fitted to a bi-exponential curve and the pharmacokinetic variables calculated using a curve stripping program (STRIPE). No significant differences were observed between groups regarding plasma sufentanil concentrations or pharmacokinetic parameters. Our results demonstrate that respiratory alkalosis and dehydration do not alter the pharmacokinetics of sufentanil after intravenous bolus administration.