Tachyphylaxis during postoperative epidural analgesia--new insights.
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Analgesia↗
Biomedical subjects
H Kehlet
Publications and source records attributed to H Kehlet.
Effect of sham-feeding on glucose tolerance and insulin secretion.
Glucose, 25 g, was infused iv with or without sham-feeding in seven normal males. Sham-feeding improved glucose tolerance, incremental area of blood glucose being 63% (P less than 0.05) of that during iv glucose without sham-feeding. The actual insulin secretion evaluated from the total area under the C-peptide and insulin curves did not differ during iv glucose with or without sham-feeding. These results suggest that the cephalic-vagal reflex improves glucose tolerance during iv glucose, independent of changes in beta-cell function.
Adult↗
Influence of neural blockade and indomethacin on leucocyte, temperature, and acute-phase protein response to surgery.
Body temperature, P-cortisol, P-glucose, P-transferrin, haematocrit and total and differential leucocyte counts were investigated in 24 men undergoing inguinal herniotomy, but otherwise healthy. The patients were randomized to general anaesthesia (GA, n = 8), epidural analgesia (E, n = 8) or epidural analgesia + indomethacin (E + I, n = 8). The rectal temperature rose significantly after surgery, except in the E + I group, and increase in blood granulocytes was significantly less in these patients than in the GA group. Group E showed intermediate changes. P-transferrin changes were similar in all three groups. Glucose and cortisol showed only slight increase in the GA group and constant values in groups E and E + I. It is concluded that prostaglandins may play a role in mediating the surgical stress response, but that factors other than neural stimuli and prostaglandins are important in releasing postoperative granulocytosis.
Acute-Phase Proteins↗
Effect of intrathecal bupivacaine on somatosensory evoked potentials following dermatomal stimulation.
The effect of spinal anesthesia with 3.6 +/- 0.1 ml (mean +/- SEM) of 0.5% bupivacaine on early (less than 150 msec) somatosensory evoked potentials (SEPs) with electrical stimulation of the L1 and S1 dermatomes was examined in 12 patients. The mean level of sensory analgesia (pinprick) was T8,9 +/- 1.0 (+/- SEM) and the mean degree of motor blockade was 1.3 +/- 0.1 (Bromage scale). Intrathecal bupivacaine significantly (P less than 0.05) decreased the amplitude of all SEP components after stimulation of the L1 dermatome and most components during stimulation of the S1 dermatome. Intrathecal bupivacaine also increased the latency of SEPs (P less than 0.05) of both dermatomes. The L1 SEP disappeared in 7 and the S1 SEPs in 5 of the 12 patients during neural blockade. In three patients the SEPs disappeared at both locations. Sensory thresholds increased significantly during blockade. We found no correlation between decrease of amplitude and degree of motor blockade or level of sensory analgesia. Thus, intrathecal plain bupivacaine has a strong depressant effect on the neural afferent transmission as assessed by SEPs. However, despite clinically effective blockade as assessed by pinprick and motor blockade nerve potentials after nociceptive stimulation within the area of sensory block were often able to pass to the cerebral cortex.
Adult↗
Fatigue and muscle amino acids during surgical convalescence.
Muscle and plasma amino acids, subjective fatigue and body weight were studied in 16 patients before and 20 days after uncomplicated elective abdominal surgery. Fatigue increased from a mean (+/- SEM) preoperative level of 2.4 +/- 0.4 arbitrary units to 4.4 +/- 0.5 on postoperative day 20, while body weight fell from 67.3 +/- 2.5 to 64.7 +/- 2.9 kg (both differences p less than 0.001). Correlation was found between increase in fatigue and fall in body weight (r = 0.56, p less than 0.05). Plasma amino acids showed little change after surgery. In muscle, the nonessential amino group taurine, asparagine, glutamate and glycine increased and histidine and arginine decreased (both p less than 0.05) postoperatively. No correlation was found between postoperative fatigue and weight loss versus changes in muscle amino acids. Some of the well-defined immediate postoperative changes in muscle amino acids thus persisted into late, otherwise uncomplicated convalescence, but postoperative fatigue was related only to weight loss--not to changes in muscle or plasma amino acids.
Adolescent↗
Effect of thoracic epidural bupivacaine on somatosensory evoked potentials after dermatomal stimulation.
The effect of epidural bupivacaine (9 ml 0.5%) analgesia on early (less than 500 msec) somatosensory evoked potentials (SEPs) with electrical stimulation of the T-10 and L-1 dermatomes was examined in eight patients. Cortical amplitudes decreased only insignificantly after stimulation of both dermatomes, despite the presence of sensory analgesia (pin prick) from T-3.5 +/- 0.4 to L-2.9 +/- 0.4 (mean +/- SEM). Latency of the SEP components remained unchanged and sensory threshold increased only insignificantly during blockade. We conclude that thoracic epidural analgesia with conventional doses of bupivacaine provides only a limited blockade of fast conducting afferent nerve fibers.
Adult↗
Effect of epidural bupivacaine on somatosensory evoked potentials after dermatomal stimulation.
The effect of lumbar epidural analgesia with plain bupivacaine, 0.5%, on early (less than 0.5 sec) somatosensory evoked potentials (SEP) to electrical stimulation of the T-10, L-1, and S-1 dermatomes and the posterior tibial nerve was examined in eight patients. A decrease of the cortical amplitude and an increase in latency were seen, most pronounced at the L-1 level, but with only minor effect on the S-1 dermatome. No correlation was found between segmental level of analgesia and decrease in amplitude of the evoked potentials. Thus despite clinically adequate surgical anesthesia, the neural pathways as assessed by SEP were incompletely blocked except at the L1 dermatome near the epidural injection site.
Adult↗
Comparative effects of intrathecal bupivacaine and tetracaine on analgesia, cardiovascular function and plasma catecholamines.
Forty otherwise healthy male patients, scheduled for elective inguinal herniotomy, were randomly allocated to spinal anaesthesia with 3 ml 0.5% hyperbaric tetracaine or bupivacaine under double-blind conditions. The extent of blockade (pin-prick and cold sensation), blood pressure and heart rate and plasma catecholamines were measured before and 5, 10, 15, 20 and 30 min after injection, before skin incision. Cephalad spread of sensory and temperature analgesia was insignificantly higher after tetracaine. The mean time taken to reach maximal spread of analgesia was 22 min in both groups. Mean arterial pressure showed a more pronounced decrease in the tetracaine group (22 vs 12%, P less than 0.009). Heart rate fell slightly and similarly in both groups, while rate-pressure product was significantly lower in the tetracaine group. The correlation between the decrease in mean arterial pressure and the cephalad spread of sensory analgesia was similar in the two groups, suggesting that at identical levels of sensory analgesia changes in blood pressure were similar after tetracaine and bupivacaine. Plasma norepinephrine and epinephrine measurements before spinal puncture and at maximal decrease in mean arterial pressure showed a depressed response to fall in blood pressure in the tetracaine group. It is concluded that spinal anaesthesia with 3 ml hyperbaric 0.5% tetracaine is followed by a more pronounced fall in blood pressure compared to an identical dose of bupivacaine. The more pronounced sympathetic blockade, confirmed by plasma catecholamine measurements, following tetracaine is probably due to a higher cephalad spread of neurogenic blockade, rather than a differential effect on sympathetic nerve fibres.
Adult↗
Variation in spread of analgesia and loss of temperature discrimination during intermittent postoperative epidural bupivacaine administration.
The proximal-distal and bilateral extent of analgesia and loss of temperature discrimination were assessed during the initial 34.5 h after major abdominal surgery in ten patients receiving intermittent epidural bupivacaine injections according to a fixed dose regimen. Segmental spread of loss of temperature discrimination was invariably larger than analgesia at all times. During the later postoperative period (24-34 h) a pronounced intra-individual variation in both proximal-distal and bilateral spread of analgesia was observed despite identical epidural injections of bupivacaine. This variation in extent of analgesia was observed during injections of both 0.5% and 0.25% bupivacaine. The explanation of this observation is unknown but it may be shifts in catheter position, a variable disposition of the local anaesthetic agent or changes in the epidural space rather than tachyphylaxis.
Aged↗
Effects of epidural analgesia on scalp-recorded somatosensory evoked potentials to posterior tibial nerve stimulation.
The effect of epidural analgesia with plain bupivacaine 0.5% on somatosensory evoked potentials (SEP) to electrical stimulation of the posterior tibial nerve was examined in six patients. Epidural analgesia significantly increased onset time and latencies of the early components in SEP, while the amplitudes decreased. These results suggest that SEP may be valuable in the objective evaluation of possible differential neural effects of local anaesthetic agents following epidural or intrathecal administration.
Adult↗
Fatigue and anxiety in surgical patients.
In 15 patients fatigue was assessed by an arbitrary scale, anxiety by the State-Trait Anxiety Inventory and concentration by various concentration tests before and 10 and 30 days after uncomplicated elective, abdominal surgery. Preoperatively, fatigue correlated to state-anxiety (r = 0.68) and trait-anxiety (r = 0.66). From pre- to postoperatively, fatigue had increased on both day 10 and day 30. State-anxiety decreased, while trait-anxiety was unchanged. Increase in fatigue 30 days after surgery correlated to increased state-anxiety (r = 0.65), but not significantly to trait-anxiety (r = 0.38). No correlation was found between increase in fatigue 30 days after surgery and the preoperative degree of state- and trait-anxiety, (r = -0.09, r = -0.29); respectively. Neither pre- nor postoperative performance during concentration tests correlated to postoperative fatigue. It is concluded that preoperative anxiety may not be decisive for the development of postoperative fatigue. Postoperative fatigue may be considered a symptom of deterioration in cardiovascular function, neuro-muscular performance and nutritional status rather than psychological factors.
Adult↗
Influence of surgery, age and serum albumin on delayed hypersensitivity.
Delayed hypersensitivity was assessed with four antigens, viz. purified protein derivative of tuberculin (PPD), Candida albicans, streptokinase/streptodornase and mumps, 48 hours before and 24 hours after elective major abdominal surgery in 24 patients. Cumulated areas of skin response were recorded on the basis of readings 24 and 48 hours after antigen stimulation. A control group of 16 patients was similarly assessed, but without surgery between the two test occasions. Retesting in this control group increased the cumulated skin response area in all patients. The respective means for the two tests were 1 290 +/- 222 to 2 330 +/- 365 mm2 (p less than 0.0001), demonstrating a pronounced booster action by the initial test. In contrast, the surgical patients showed a decrease, from 1 559 +/- 203 preoperatively to 1 230 +/- 210 mm2 postoperatively (p = 0.14). The postoperative response was significantly lower than the retesting response in the controls without surgery (p = 0.02), indicating that surgery leads to depression of delayed hypersensitivity response. The preoperative cumulated skin test response correlated with age (r = -0.66, p less than 0.001) and with serum albumin (r = 0.59, p less than 0.01). Postoperative depression of the skin test response also was related to age (r = 0.53, p less than 0.01) and with postoperative fall in s-albumin (r = 0.51, p less than 0.05). The results emphasize that interpretation of serial skin testing in surgical patients is not adequate unless comparison is made with a similar retesting regimen in nonsurgical patients.
Aged↗
Epidural morphine improves pain relief and maintains sensory analgesia during continuous epidural bupivacaine after abdominal surgery.
Twenty patients scheduled for elective major abdominal surgery were matched into two groups with regard to age, sex, height, body weight, and surgical procedure. Both groups received general anesthesia plus lumbar epidural analgesia with similar loading doses of bupivacaine 0.5% (23.1 +/- 1.0 and 23.3 +/- 0.8 ml) (mean +/- SEM) followed by continuous infusion of plain bupivacaine 0.5% (8 ml/hr) plus, in one group, epidural morphine (0.5 mg/hr). Pain score on a 5-point scale and sensory analgesia (pin prick) were assessed hourly for 16 hours after skin incision. If sensory analgesia decreased more than 5 segments from preoperative levels or if pain scores reached 2 (moderate pain), the patients were removed from the study, and pain was treated with other methods. Preoperative mean (+/- SEM) sensory levels of analgesia were similar in the bupivacaine and the bupivacaine-morphine groups (T3.4 +/- 0.5 and T3.3 +/- 0.4, respectively). In the group receiving only bupivacaine, sensory analgesia regressed over time with a simultaneous increase in pain score. Thus, within 10 hr after skin incision, seven patients in this group were discharged from the study, and 16 hr after incision only one patient maintained initial level of sensory analgesia. In contrast, each patient receiving bupivacaine plus morphine had stable sensory analgesia and was completely free of pain as indicated by a mean pain score of zero during the 16-hr observation period. Thus epidural morphine may improve pain relief and maintain analgesia during continuous epidural bupivacaine administration after abdominal surgery.
Abdomen↗
[Cryoanalgesia. Pain relief following local application of cold].
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Humans↗
Systemic morphine enhances spread of sensory analgesia during postoperative epidural bupivacaine infusion.
Eight patients undergoing abdominal surgery received epidural analgesia with 0.5% plain bupivacaine at a fixed dose rate (8 ml/h) for postoperative pain relief. Mean sensory level of analgesia (pin prick) was assessed hourly and regressed from a mean preoperative level of T3.7 (+/- 0.3 SEM) to T10 (+/- 0.7) at an average of 8.9 +/- 1.4 h post skin incision (range 4-16 h). Simultaneously, pain scores (4-point scale) increased from zero to 2.1 +/- 0.2. When analgesia regressed greater than or equal to 5 segments, administration of 10 mg morphine intravenously led to a pronounced cephalad increase in sensory analgesia; the initial level of analgesia was achieved in every case despite unchanged bupivacaine infusion. Simultaneously, pain score decreased to 0.3 +/- 0.3. This synergistic effect of systemic morphine on the extent of neural blockade with epidural bupivacaine may have an important role in improving postoperative pain relief.
Adult↗
Influence of pre- and intra- operative factors on the occurrence of postoperative fatigue.
Subjective feeling of fatigue was assessed before and 10, 20 and 30 days after uncomplicated abdominal surgery in 52 patients and after minor otological surgery in 15 patients. In major surgery fatigue increased from 3.0 +/- 0.2 (mean +/- s.e.m.) arbitrary units pre-operatively to 6.1 +/- 0.3, 5.3 +/- 0.3 and 4.1 +/- 0.3 on day 10, 20 and 30, respectively (P less than 0.001). In contrast, after minor surgery fatigue did not change from before surgery (2.1 +/- 0.3) to day 7 (2.9 +/- 0.5) (P greater than 0.05), day 20 (2.3 +/- 0.4) (P greater than 0.4), or day 30 after surgery (2.1 +/- 0.3) (P greater than 0.9). Differences in fatigue between groups were significant postoperatively (P less than 0.001), but not preoperatively (P greater than 0.05). Mean duration of surgery was similar in the two groups. In the abdominal group an increase in postoperative fatigue did not correlate with age, sex, pre-operative degree of fatigue, actual body weight, triceps skinfold thickness (TSF), arm muscle circumference (AMC), anthropometric index (body weight X TSF X AMC) or serum-transferrin, but did slightly with pre-operative body weight related to ideal body weight (r = -0.3, P less than 0.05). Thus, the magnitude of the trauma and not the duration of anaesthesia may be important for occurrence of postoperative fatigue. Furthermore, fatigue after elective abdominal surgery seems to be unpredictable from the pre-operative status of the patient.
Age Factors↗
Influence of diabetes mellitus on operative risk.
In a retrospective study postoperative morbidity was compared between 224 patients with diabetes mellitus and 224 non-diabetic control patients matched with regard to operative procedure (major vascular, abdominal and acute surgery for hip fracture), sex, age, complicating cardiovascular disease and weight. Forty-six patients in each group had complications, without any trend towards specific morbidity in the diabetic group. Incidence of morbidity was similar in diabetic patients treated with insulin, oral antidiabetic agents or diet. Diabetic patients with complications had significantly (P less than 0.01) lower blood glucose pre- and postoperatively than those without complications. The risk of overlooking (type II error) a 25 per cent increase in complication rate in the diabetic patients was less than 10 per cent and the risk of overlooking a 50 per cent increase in morbidity less than 0.5 per cent. These results do not support the common belief that diabetes per se may increase surgical risk.
Aged↗