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Biomedical subjects

H Kehlet

Publications and source records attributed to H Kehlet.

At least 271 records · Page 15Linked to original sources
PubMed1989

[Immunologic consequences of surgery, anesthesia and blood transfusion. Surgical immunosuppression].

On the basis of the literature and the authors own investigations, the present article provides a brief schematic review of the fraction of the physiological immune response which has hitherto been investigated in connection with surgical trauma. Surgery, anaesthesia and blood transfusion induce temporarily acquired immune suppression and thus a potentially increased risk for postoperative infectious complications and recurrence after cancer surgery. The pathological physiological alterations in immune function which develop as a result of anaesthesia, surgery and perioperative blood transfusion are reviewed. The clinical sequelae of preoperative and postoperative immune suppression are increased morbidity and mortality rates. Future research in this field must, therefore, be focussed on detailed investigation of the mechanisms which lead to postoperative immune suppression and development of methods to prevent these.

Anesthesia↗
PubMed1989

[Colloids versus crystalloids in the treatment of hypovolemic or septic shock].

The literature is reviewed with the aim of comparing the effect of resuscitation with colloid solutions with that of crystalloid solutions in the following patient categories: patients undergoing major elective abdominal surgery, patients in hypovolemic shock due to acute trauma and patients in septic shock. None of the clinical trials have documented that resuscitation with colloids is superior to that of crystalloids alone as regards mortality or frequency of complications. On the contrary, colloid resuscitation appears to be detrimental in patients with traumainduced hypovolemic shock with a higher incidence of pulmonary and cardiac complications as compared to resuscitation with crystalloids alone. This is contrary to what is expected from the Starling equation and the discrepancy between the theoretical and clinical findings is discussed. Furthermore, resuscitation with colloids is about 50 times more expensive than resuscitation with crystalloids. On the basis of the clinical data and the higher cost of colloids, the authors recommend cessation of the use of colloids in the abovementioned conditions.

Colloids↗
PubMed1989

[Physiology and physiopathology of defecation].

The normal physiology of defaecation is reviewed with the object of understanding pathological defaecation. The significance of investigation of anorectal physiology in cases of disturbance of defaecation is emphasized in view of further understanding of the basic mechanisms and offers of rational therapy.

Anal Canal↗
PubMed1989

Ranitidine for prevention of postoperative suppression of delayed hypersensitivity.

Cell-mediated immunity was assessed by skin testing with seven delayed-type common antigens in 20 patients undergoing major abdominal surgery and in 20 nonoperative control subjects. The 20 surgical patients were randomized to perioperative ranitidine (50 mg every 6 hours for 72 hours) or no ranitidine. The 20 control subjects received either no ranitidine or ranitidine in the same dosage as the surgical patients. Skin tests were performed 2 days before and 1 day after operation with the same time schedule in the control subjects. Postoperatively, the diameter of the positive skin test area decreased in each of 10 patients without ranitidine (p less than 0.006) but increased in 9 and was unchanged in 1 of the ranitidine-treated patients (p less than 0.01). The skin test changes were similar during the two tests in ranitidine-treated surgical patients and the nonoperative control subjects. Ranitidine did not amplify the response in the nonoperated group. The potential role of histamine blockade in reversal of other aspects of postoperative immunosuppression and reduction in the risk of infection should be explored.

Adult↗
PubMed1989

Continuous thoracic extradural 0.5% bupivacaine with or without morphine: effect on quality of blockade, lung function and the surgical stress response.

Twenty-two patients undergoing upper abdominal surgery were entered into a randomized, double-blind study to receive extradural (T7-T8) 0.5% bupivacaine 9 ml followed by 25 mg h-1 with or without additional extradural morphine (bolus 4 mg plus 0.5 mg h-1), for 16 h after operation. Addition of morphine was associated with total alleviation of pain, and a stable level of sensory analgesia, but not with changes in blood glucose and cortisol concentrations or postoperative impairment of lung function (PEFR, FEV1, FVC). Two patients were withdrawn because of hypotension or respiratory depression.

Analgesia, Epidural↗
PubMed1989

Comparison of the effects of extradural clonidine with those of morphine on postoperative pain, stress responses, cardiopulmonary function and motor and sensory block.

We have examined the effects of extradural clonidine 150 micrograms or morphine 4 mg on postoperative pain, stress responses, cardiopulmonary function and motor and sensory block in a double-blind, randomized study in 20 patients undergoing hysterectomy with general anaesthesia. Observations were made for 6 h after each patient's first request for analgesia. Clonidine provided greater pain relief than morphine only for the first 2 h of observation (P less than 0.001). Plasma cortisol concentrations decreased to a greater extent (P less than 0.05) with morphine, while plasma glucose concentration increased by a similar extent in both groups. After clonidine, mean arterial pressure decreased from 100 (SEM 3) mm Hg to 70 (3) mm Hg (P less than 0.05), but there was no change after morphine. There were no significant changes in heart rate, pulmonary function (FEV1), motor function or sensory analgesia to touch, temperature and pinprick in both groups. Additional systemic opioids were required by five and six patients in the clonidine and morphine groups, respectively.

Adult↗
PubMed1989

Episodic arterial oxygen desaturation and heart rate variations following major abdominal surgery.

In 20 patients undergoing elective major abdominal surgery, heart rate and arterial oxygen saturation were monitored continuously during the night 2 days before operation and during the first and second nights after operation (23:00 to 07:30). Mean heart rate increased by 16 beat min-1 (P less than 0.0006) and mean oxygen saturation decreased by 3.2% (P less than 0.0002) after operation. Four patients had 21, 27, 120 and 372 episodes of sudden desaturation to a value less than 80% on the second night after operation. The patient with 372 episodes of sudden desaturation had severe cardiac arrhythmias on the morning of the third day after operation. In another patient the episodes of desaturation correlated with increases in heart rate. There was no correlation between administration of opioids and heart rate and saturation disturbances. The mechanism and clinical relevance of episodic desaturation in the late postoperative period remain unknown, but may be important in the pathogenesis of post-operative cardiac, cerebral and wound dysfunction.

Abdomen↗
PubMed1989

Comparison of the effects of continuous intrapleural vs epidural administration of 0.5% bupivacaine on pain, metabolic response and pulmonary function following cholecystectomy.

Twenty patients undergoing elective cholecystectomy were prospectively randomised to receive either intrapleural (bolus 20 ml followed by 10 ml/h) or thoracic epidural (bolus 9 ml followed by 5 ml/h) bupivacaine 0.5% for 8 h postoperatively to assess the effect of these two techniques on pain, pulmonary function and the surgical stress response. As assessed by the visual analogue scale (VAS), both groups received good but not total pain relief. Both groups had a 50% reduction in forced expiratory volume (FEV1), forced vital capacity (FVC) and peak expiratory flow rate (PEFR) after operation, and there was no observed effect on the stress response as measured by plasma glucose and cortisol. It is concluded that while both techniques provide good analgesia, the degree and extent of nerve blockade are not sufficient to affect the afferent neurogenic stimuli responsible for the observed effects on pulmonary function and the stress response.

Adult↗
PubMed1989

Effects of thoracic paravertebral block with bupivacaine versus combined thoracic epidural block with bupivacaine and morphine on pain and pulmonary function after cholecystectomy.

Twenty patients undergoing elective cholecystectomy via a subcostal incision were randomized in a double-blind study to either thoracic paravertebral blockade with bupivacaine 0.5% (15 ml followed by 5 ml/h) or thoracic epidural blockade with bupivacaine 7 ml 0.5% + morphine 2 mg followed by 5 ml/h + 0.2 mg/h, respectively for 8 h postoperatively. Mean initial spread of sensory analgesia on the right side was the same (Th3,4-Th11 versus Th2,6-Th11), but decreased (P less than 0.05) postoperatively in the paravertebral group. All patients in the epidural group had bilateral blockade, compared with three patients in the paravertebral group. In both groups only minor insignificant changes in blood pressure and pulse rate were seen postoperatively. Pain scores were significantly higher in the paravertebral group, as was the need for systemic morphine (P less than 0.05). Pulmonary function estimated by forced vital capacity, forced expiratory volume and peak expiratory flow rate decreased about 50% postoperatively in both groups. In conclusion, the continuous paravertebral bupivacaine infusion used here was insufficient as the only analgesic after cholecystectomy. In contrast, epidural blockade with combined bupivacaine and low dose morphine produced total pain relief in six of ten patients.

Adult↗
PubMed1989

Anesthetic technique and surgical convalescence.

This brief review presents an update of studies on postoperative fatigue and convalescence and the way in which they are affected by anesthetic technique. Development of postoperative fatigue is related to the degree of surgical trauma, but not to general anesthesia, and it cannot be predicted from age, sex, duration of surgery, or preoperative assessment of various nutritional parameters. Postoperative fatigue correlates with deterioration in nutritional status and impaired adaptability of heart rate to orthostatic stress and bicycle exercise. Decreases in muscle performance and endurance are associated with postoperative fatigue, but psychological factors such as preoperative degree of anxiety do not appear to be important factors. Pain relief with regional anesthetics does not improve postoperative fatigue after abdominal surgery; however, no studies are available that evaluate the effects of regional analgesia with concomitant inhibition of the stress response. Controlled studies suggest that the use of regional anesthesia with local anesthetics reduces duration of hospitalization and time to ambulation. Further studies are needed to define the relative roles of immobilization, impaired nutritional intake, and surgical stress response in the pathogenesis of postoperative fatigue.

Anesthesia, Conduction↗
PubMed1989

The stress response to surgery: release mechanisms and the modifying effect of pain relief.

This short review updates information on the release mechanisms of the systemic response to surgical injury and the modifying effect of pain relief. Initiation of the response is primarily due to afferent nerve impulses combined with release of humoral substances (such as prostaglandins, kinins, leukotrienes, interleukin-1, and tumor necrosis factor), while amplification factors include semi-starvation, infection, and hemorrhage. The relative role of the various signals in producing the complex injury response has not been finally determined, but the neural pathway is probably most important in releasing the classical endocrine catabolic response, while humoral factors are important for the hyperthermic response, changes in coagulation and fibrinolysis immunofunction, and capillary permeability. The modifying effect of pain relief on the surgical stress response is dependent upon the technique of analgesia. However, the effect on humoral-mediated responses is small, regardless of the technique used. Afferent neural blockade with local anesthetics is the most effective technique for reducing the endocrine-metabolic response, but only in operations in the lower part of the abdomen, probably because of insufficient afferent blockade during thoracic epidural analgesia. Systemic opiate administration, as well as non-steroidal antiinflammatory drugs, exert only a small modifying effect on the response. Low-dose combined analgesic regimens may provide total pain relief, but exert no important effect on the stress response. In summary, pain alleviation itself may not necessarily lead to an important modification of the stress response, and a combined approach with inhibition of the neural and humoral release mechanisms is necessary for a pronounced inhibition or prevention of the response to surgical injury.

Analgesia↗
PubMed1989

Ranitidine prevents postoperative transfusion-induced depression of delayed hypersensitivity.

The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common delayed-type antigens in 83 consecutive patients undergoing major elective abdominal surgery. Sixty-six of these patients were randomly divided into ranitidine or no-ranitidine-treatment groups, and the remaining 17 patients were operated on without ranitidine. Thus, 50 patients were operated on without ranitidine therapy, and whole blood transfusion was given to 24 of these patients. Postoperative skin test response was more reduced in transfused vs nontransfused patients (-57% vs -38%, p less than 0.0001). Fourteen of the 24 patients receiving blood transfusion could be exactly matched to 14 patients not receiving transfusion (age, sex, B-hemoglobin, S-albumin, type and duration of surgery, etc.), which confirmed that a more pronounced reduction in postoperative skin test response was found in transfused patients (-55% vs -31%, p less than 0.0001). Seventeen of the 33 patients treated with perioperative ranitidine, 50 mg intravenously every 6 hours for 72 hours, received perioperative blood transfusion. Eleven of these patients could be matched to 11 transfused patients not receiving perioperative ranitidine. Ranitidine prevented postoperative reduction in skin test response (+6% vs -55%, p less than 0.0001). It is concluded that perioperative transfusion with whole blood amplifies the postoperative impairment in delayed hypersensitivity and that transfusion-induced postoperative impairment in delayed hypersensitivity may be prevented by perioperative ranitidine treatment.

Abdomen↗
PubMed1989

Tachyphylaxis associated with repeated epidural injections of lidocaine is not related to changes in distribution or the rate of elimination from the epidural space.

The relationship between tachyphylaxis (measured as a decrease in the rate of regression of sensory levels of analgesia) during repeated epidural injections of lidocaine and both the distribution of lidocaine within the epidural space (as measured by spread of simultaneous injection of the tracer technetium-99m diethylenetriaminepentaacetate [99mTc-DTPA]) and elimination of lidocaine from the epidural space (as measured by serum concentrations of lidocaine) was investigated in 18 patients undergoing minor surgery during lumbar epidural analgesia. Twelve patients received four injections of 20 mL of 2% lidocaine at 2-hr intervals. Epidural distribution was assessed by injection of 99mTc-DTPA diluted in saline on the preoperative day and diluted in an equal volume of 2% lidocaine on the morning before surgery and again after the fourth injection of lidocaine 6 hr later. The distribution of 99mTc-DTPA in the epidural space was unchanged during the three measurements despite significant tachyphylaxis in both sensory analgesia and motor blockade (11 of 12 patients had sensory analgesia 2 hr after the first injection in contrast to only 3 of 12 patients during the third injection). In another six patients 20 mL of 2% lidocaine were injected three times at 2-hr intervals before surgery, with measurements of serum concentrations of lidocaine after the first and last injections. Despite tachyphylaxis (no patient had sensory analgesia 2 hr after the third injection), there was no difference in the rate of disappearance of lidocaine from the epidural space as assessed by plasma lidocaine concentration curves during the first and third injection (0.5 +/- 0.1 and 0.3 +/- 0.04 microgram.mL-1.min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Effect of ranitidine on postoperative suppression of natural killer cell activity and delayed hypersensitivity.

In a randomized study of patients undergoing major elective abdominal surgery, 12 received i.v. ranitidine (50 mg every 6 hours for 72 hours from the skin incision) and 12 had no ranitidine. Cell-mediated immunity was assessed pre- and postoperatively by skin testing with seven common delayed type hypersensitivity (DTH) antigens, and blood drawn immediately before and 24 hours after skin incision was analyzed for spontaneous and in vitro stimulated (IL-2, IFN-alpha or indomethacin) natural killer (NK) cell activity and PHA and PPD-stimulated lymphocyte proliferation. Lymphocyte subsets (helper/inducer-T cells, suppressor/cytotoxic-T cells, Pan-T cells and NK-cells) were counted by flow-cytometry. Perioperative ranitidine diminished the expected postoperative reduction in DTH responses (p less than 0.0001), as well as in spontaneous NK-cell activity (p less than 0.03) and in vitro IL-2 stimulated NK-cell activity (p less than 0.02). Postoperative decrease in helper/inducer-T cell numbers was not significantly lessened (p = 0.07), and ranitidine did not influence the levels of suppressor-T cells. PHA and PPD responses in peripheral blood mononuclear cells were unaltered. The results may suggest potential benefit from ranitidine as regards postoperative infectious complications and recurrence of malignancy.

Abdomen↗
PubMed1989

Ranitidine for improvement of delayed hypersensitivity response in patients with sepsis.

Twenty-five patients admitted to intensive or high-dependency surgical care units were randomized to receive ranitidine intravenously 50 mg every 6 hours for 8 days or no ranitidine. All had septicemia or intra-abdominal sepsis, with body temperature greater than or equal to 38.5 degrees C for more than 48 hours despite comprehensive medical and/or surgical treatment. Cell-mediated immunity was assessed by skin testing with seven common delayed type hypersensitivity antigens applied on days 1, 4 and 7 and all tests were read at 48 hours, i.e. on days 3, 6 and 9. The ranitidine/non-ranitidine regimen was initiated on day 1 and continued until day 9. Severity of illness was evaluated before and 3, 6 and 8 days after initiating the study, using the APACHE II scoring system. The scores before and during the study were similar in the ranitidine and non-ranitidine groups. Delayed type hypersensitivity improved in patients treated with ranitidine (p less than 0.001), but was unchanged in the untreated group (p greater than 0.7). These observations may suggest potential beneficial effects of ranitidine therapy in patients with trauma-induced immunosuppression.

Adult↗
PubMed1989

Effect of epidural clonidine on somatosensory evoked potentials to dermatomal stimulation.

The effect of lumbar epidural clonidine 150 micrograms on early (less than 0.5 s) somatosensory evoked potentials (SEP) to electrical stimulation of the L1 and S1 dermatomes was examined in twelve cancer patients. Epidural clonidine led to a minor but significant decrease in amplitude of two components (N1 and N3) following S1 stimulation while SEP latency was prolonged only in the P1 and P3 components (P less than 0.05). In all patients the pain score decreased, mean score at rest from 4.9 +/- 0.5 to 0.6 +/- 0.2 and during mobilization from 7.4 +/- 0.6 to 1.3 +/- 0.5 (P less than 0.01). Mean systolic and diastolic blood pressures decreased from 118 +/- 4/72 +/- 5 mmHg to 99 +/- 5/60 +/- 3 mmHg (P less than 0.01), respectively. It is concluded that epidural clonidine has a minor effect on the early SEPs to electrical dermatomal stimulation. Additionally, a pronounced effect on cancer pain was seen.

Aged↗