[Anaesthetics and porphyria].

Patients with acute porphyria are at risk of life-threatening attacks when exposed to stress, fast, infection, alcohol and especially some drugs, including older anaesthetics. Acute porphyrias are rare inherited diseases caused by inefficient enzymatic activity within the haem synthesis. During attacks the patient suffers from severe abdominal pain, cardiovascular instability, neurological symptoms etc. Preventive measures and treatment should be known to anaesthesiologists and surgeons in particular and known to other clinicians in general. In order to assist the clinicians, drug databases are available online.

Postoperative recovery profile after elective abdominal hysterectomy: a prospective, observational study of a multimodal anaesthetic regime.

BACKGROUND AND OBJECTIVE: To evaluate the applicability, effectiveness, immediate postoperative complaints and requirements for a postanaesthesia care unit stay after elective abdominal hysterectomy under a well defined, multimodal anaesthetic regime. METHODS: Observational study of 145 consecutive patients scheduled for the procedure at a major university hospital in Denmark. Perioperative treatments and postoperative complaints were recorded continuously until discharge from the postanaesthesia care unit. Main outcome measures were treatment regimen adherence, pain, nausea and vomiting, respiratory insufficiency and time of discharge readiness. RESULTS: The structured regime consisting of total intravenous anaesthesia (propofol-remifentanil), well defined fluid administration, prophylactic antiemetics (dexamethasone, ondansetron, droperidol), weak analgesics (celecoxib, paracetamol) and intraoperative epidural analgesia (bupivacaine, morphine) was feasible in more than 90% of all patients. In the postanaesthesia care unit, 64% did not require opioids, but 25% experienced severe pain. Mean length of stay was 2 h with a mean discharge readiness of 80 min. Half the patients required supplemental oxygen for 1 h or more to sustain an SpO2 greater than 92%, and 8% experienced nausea or vomiting. A complicated recovery, defined as the presence of severe complaints (pain, nausea or vomiting), with more than five treatment interventions in the postanaesthesia care unit, or a length of stay more than 2 h, was seen in 52%. CONCLUSION: We conclude that a structured multimodal anaesthetic regime is feasible in daily clinical practice and advantageous, and that postoperative pain and oxygen requirements (to sustain an SpO2 >92%) are the major determinants for length of stay in the postanaesthesia care unit. Further research should focus on nonopioid analgesic systemic adjuvants to improve early recovery and reduce stay in the postanaesthesia care unit.

[Medical emergency teams]. / Mobilt akutteam.

The aim of medical emergency teams (MET) is to identify and treat deteriorating patients on general wards, and to avoid cardiac arrest, unplanned intensive care unit admission and death. The effectiveness of METs has yet to be proven, as the only two randomised, controlled trials on the subject show conflicting results. Despite the lack of evidence, METs are gaining popularity and are being implemented in Danish hospitals as part of Operation Life.

Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits.

OBJECTIVES: To evaluate the effect of estrogen replacement therapy or soy isoflavones supplement on endothelium-dependent relaxation in vitro and gene expression of endothelial nitric oxide synthase (eNOS) in cerebral arteries in a rabbit model of human hypercholesterolemia. STUDY DESIGN: Thirty-six female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomised to treatment with 17beta-estradiol (17beta-E(2)), SoyLife 150 or control for 16 weeks. Ring segments of basilar artery (BA) and posterior cerebral artery (PCA) were mounted in myographs for isometric tension recordings. Concentration response curves to carbamylcholine chloride, sodium nitroprusside (SNP) and l-NAME were evaluated after precontraction with potassium. Total RNA was extracted, reverse transcribed and eNOS quantitated by real-time polymerase chain reaction (real-time PCR). RESULTS: Plasma cholesterol was significantly higher at termination in the SoyLife group (P<0.0001), whereas low-density lipoprotein (LDL) cholesterol was comparable in all treatment groups. Neither treatment influenced the endothelium-dependent responses to carbamylcholine chloride or l-NAME or the endothelium-independent response to SNP in any of the arteries. Correspondingly, eNOS mRNA was similarly expressed in all treatment groups in both arteries. CONCLUSIONS: Improvement of cerebral endothelial function by estrogen or soy isoflavones in ovariectomized WHHL rabbits is not supported by the present data. The findings may be unique to the WHHL rabbit in which the hypocholesterolemic effect of estrogens mediated by upregulation of liver LDL receptors is excluded.

[Outpatient laparoscopic cholecystectomy--two years of experience]. / Ambulant laparoskopisk kolecystektomi--to års erfaring.

INTRODUCTION: By careful selection of both patients and surgeon, outpatient laparoscopic cholecystectomy can be performed in up to 90% of elective patients. The rate of same-day discharge in an unselected group scheduled for elective operation is, however, not clarified. MATERIALS AND METHODS: A clinical pathway for outpatient laparoscopic cholecystectomy was introduced as the standard procedure for all patients undergoing elective operation. The set-up allowed easy access to an overnight stay if needed. Hospital stay, complications, reasons for admittance, the need for medical advice after discharge, convalescence and patients" satisfaction were analysed. Prospective registrations were undertaken in a standard care plan, and a questionnaire was sent out after four weeks. RESULTS: During two years of the study, 535 patients had a cholecystectomy done. Of these, 403 were scheduled for elective laparoscopic operation and entered the clinical pathway. In 62% of the patients, the outpatient course was successfully completed, and 94% of the patients were discharged within 24 hours. In 2%, complications resulted in hospital stays longer than three days, and 2.7% of the operations were converted. About one third of the patients needed additional medical advice after discharge, and 4.3% of these were readmitted. Pain was among the most frequent complaints. The patients" satisfaction with the procedure was approximately 90%. DISCUSSION: In an unselected group of patients scheduled for elective laparoscopic cholecystectomy, about two thirds can be treated as outpatients with a high degree of safety and patients" satisfaction. Further development, especially in the multimodal treatment of pain, is still the most important area to focus on in order to reduce postoperative complaints and improve the course of convalescence.

Functional recovery after open versus laparoscopic colonic resection: a randomized, blinded study.

BACKGROUND: Laparoscopic colonic surgery has been claimed to hasten recovery and reduce hospital stay compared with open operation. Recently, enforced multimodal rehabilitation (fast-track surgery) has improved recovery and reduced hospital stay in both laparoscopic and open colonic surgery. Since no comparative data between laparoscopic and open colonic resection with multimodal rehabilitation are available, the value of laparoscopy per se is unknown. METHODS: In a randomized, observer-and-patient, blinded trial, 60 patients (median age 75 years) underwent elective laparoscopic or open colonic resection with fast-track rehabilitation and planned discharge after 48 hours. Functional recovery was assessed in detail during the first postoperative month. RESULTS: Median postoperative hospital stay was 2 days in both groups, with early and similar recovery to normal activities as assessed by hours of mobilization per day, computerized monitoring of motor activity assessed, pulmonary function, cardiovascular response to treadmill exercise, pain, sleep quality, fatigue, and return to normal gastrointestinal function. There were no significant differences in postoperative morbidity, mortality, or readmissions, although 3 patients died in the open versus nil in the laparoscopic group. CONCLUSION: Functional recovery after colonic resection is rapid with a multimodal rehabilitation regimen and without differences between open and laparoscopic operation. Further large-scale studies are required on potential differences in serious morbidity and mortality.

Progestins used in hormonal replacement therapy display different effects in coronary arteries from New Zealand white rabbits.

OBJECTIVES: The aim of this study was in an animal model to assess the vascular effects of different progestins commonly used in hormonal replacement treatment. METHODS: Fifty-six non-atherosclerotic, ovariectomized New Zealand white rabbits were randomized into seven groups: (1) medroxyprogesterone acetate (MPA), (2) norethisterone acetate (NETA), (3) conjugated equine estrogens (CEE), (4) 17-beta-estradiol (E2), (5) MPA+CEE , (6) NETA+E2 , (7) or placebo (n=8) and given hormonal treatment through the diet for 4 weeks. Ring segments from the left proximal coronary artery and from the distal part of the left anterior descending coronary artery were microdissected and mounted for isometric tension recordings in a myograph. The vasoconstrictory responses induced by potassium, endothelin-1, calcium and Nw-nitro-L-arginine methyl ester, and the vasodilatory response induced by acetylcholine and sodiumnitroprusside were investigated. The maximum contraction/relaxation (Emax) and the concentration required to induce half the maximum response (EC50) were determined. EC50 values were expressed as the negative logarithm to the molar concentration, pD2=-log EC50. RESULTS: Treatment with MPA alone caused when compared to treatment with NETA an increase in tension development in the distal coronary artery after the addition of potassium ( 6.36+/-0.36 versus 4.31+/-0.42 P<0.005) (single dose response, mN/mm, mean+/-S.E.M.) and endothelin-1 (9.41+/-0.82 versus 6.43+/-0.73 P<0.05) (Emax, mN/mm, mean+/-S.E.M.). Treatment with MPA compared to placebo caused an endothelin-1 induced increase of Emax in the distal coronary artery (9.21+/-0.87 versus 6.51+/-0.65 P<0.05) and a calcium induced increase of pD2 in both coronary arteries (2.98+/-0.19 versus 2.42+/-0.12 P<0.05, proximal coronary artery) (3.26+/-0.09 versus 2.9+/-0.1 P<0.05, distal coronary artery) (pD2, mean+/-S.E.M.). Treatment with NETA compared to placebo in the proximal coronary artery, after the addition of sodiumnitroprusside caused a decrease of pD2 (5.33+/-0.19 versus 5.94+/-0.13 P<0.05). Treatment with E2 compared to treatment with CEE in the proximal coronary artery caused a decrease of pD2 after the addition of sodiumnitroprusside (5.00+/-0.16 versus 5.77+/-0.28 P<0.05). No significant differences were found between MPA+CEE and NETA+E2. CONCLUSION: Treatment with MPA alone seems to enhance the contractile response to potassium and endothelin-1 in the distal coronary artery compared to NETA, indicating that different progestins used in hormonal replacement treatment may display different effects on contractile functions of coronary arteries.

Liberal versus restrictive fluid administration to improve recovery after laparoscopic cholecystectomy: a randomized, double-blind study.

OBJECTIVE: The objective of this study was to investigate the effects of 2 levels of intraoperative fluid administration on perioperative physiology and outcome after laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: Intraoperative fluid administration is variable as a result of limited knowledge of physiological and clinical effects of different fluid substitution regimens. METHODS: In a double-blind study, 48 ASA I-II patients undergoing laparoscopic cholecystectomy were randomized to 15 mL/kg (group 1) or 40 mL/kg (group 2) intraoperative administration of lactated Ringer's solution (LR). All other aspects of perioperative management as well as preoperative fluid status were standardized. Primary outcome parameters were assessed repeatedly for the first 24 postoperative hours and included pulmonary function (spirometry), exercise capacity (submaximal treadmill test), cardiovascular hormonal responses, balance function, pain, nausea and vomiting, recovery, and hospital stay. RESULTS: Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR led to significant improvements in postoperative pulmonary function and exercise capacity and a reduced stress response (aldosterone, antidiuretic hormone, and angiotensin II). Nausea, general well-being, thirst, dizziness, drowsiness, fatigue, and balance function were also significantly improved, as well as significantly more patients fulfilled discharge criteria and were discharged on the day of surgery with the high-volume fluid substitution. CONCLUSIONS: Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR improves postoperative organ functions and recovery and shortens hospital stay after laparoscopic cholecystectomy.

Tibolone and its metabolites acutely relax rabbit coronary arteries in vitro.

OBJECTIVES: To compare the acute effects of estradiol, tibolone and its metabolites on coronary arteries in vitro and to investigate possible vascular mechanisms. METHODS: Coronary artery ring segments from female rabbits were mounted in myographs for isometric tension recordings. Concentration-response curves to tibolone, 3 alpha-OH-tibolone, 3 beta-OH-tibolone, Delta 4-isomer and 17 beta-estradiol were obtained after precontraction with potassium 30 mmol/l and after addition of N omega-nitro-l-arginine methyl ester 10(-4) mol/l (l-NAME, an inhibitor of endothelial nitric oxide (NO) synthase) or tetraethylammonium chloride 10(-2) mol/l (TEA, an unspecific inhibitor of potassium channels). The effects of the different substances to calcium concentration-response curves were evaluated. Responses are expressed as maximal contraction (E max), concentration giving half maximal contraction (log EC50) or area under curve (AUC). RESULTS: Tibolone and its metabolites induced a concentration-dependent vasodilatation comparable to that of 17 beta-estradiol with the rank of potency: 3 beta-OH-tibolone approximately = to tibolone>3 alpha-OH-tibolone>Delta 4-isomer (ANOVA). l-NAME partly inhibited the relaxation to all substances. TEA induced a slight rightward shift of the relaxation to 3 alpha-OH-tibolone (log EC50: -5.05 versus -5.20; P<0.05; Student's t-test), but not to the other substances. Calcium concentration-dependent contraction curves were inhibited by all substances compared to controls (AUC, P<0.05, ANOVA). CONCLUSIONS: Our data indicate that the acute relaxation induced by tibolone and its metabolites in coronary arteries in vitro are probably mediated by endothelium independent inhibition of calcium channels but may also involve an endothelium-dependent mechanism via nitric oxide. The effect of tibolone is comparable to that of 17 beta-estradiol in this set-up.

Epidural anesthesia, hypotension, and changes in intravascular volume.

BACKGROUND: The most common side effect of epidural or spinal anesthesia is hypotension with functional hypovolemia prompting fluid infusions or administration of vasopressors. Short-term studies (20 min) in patients undergoing lumbar epidural anesthesia suggest that plasma volume may increase when hypotension is present, which may have implications for the choice of treatment of hypotension. However, no long-term information or measurements of plasma volumes with or without hypotension after epidural anesthesia are available. METHODS: In 12 healthy volunteers, the authors assessed plasma (125I-albumin) and erythrocyte (51Cr-EDTA) volumes before and 90 min after administration of 10 ml bupivacaine, 0.5%, via a thoracic epidural catheter (T7-T10). After 90 min (t = 90), subjects were randomized to administration of fluid (7 ml/kg hydroxyethyl starch) or a vasopressor (0.2 mg/kg ephedrine), and 40 min later (t = 130), plasma and erythrocyte volumes were measured. At the same time points, mean corpuscular volume and hematocrit were measured. Systolic and diastolic blood pressure, heart rate, and hemoglobin were measured every 5 min throughout the study. Volume kinetic analysis was performed for the volunteers receiving hydroxyethyl starch. RESULTS: Plasma volume did not change per se after thoracic epidural anesthesia despite a decrease in blood pressure. Plasma volume increased with fluid administration but remained unchanged with vasopressors despite that both treatments had similar hemodynamic effects. Hemoglobin concentrations were not significantly altered by the epidural blockade or ephedrine administration but decreased significantly after hydroxyethyl starch administration. Volume kinetic analysis showed that the infused fluid expanded a rather small volume, approximately 1.5 l. The elimination constant was 56 ml/min. CONCLUSIONS: Thoracic epidural anesthesia per se does not lead to changes in blood volumes despite a reduction in blood pressure. When fluid is infused, there is a dilution, and the fluid initially seems to be located centrally. Because administration of hydroxyethyl starch and ephedrine has similar hemodynamic effects, the latter may be preferred in patients with cardiopulmonary diseases in which perioperative fluid overload is undesirable.

Improved fertility following conservative surgical treatment of ectopic pregnancy.

OBJECTIVE: To evaluate fertility after salpingectomy or tubotomy for ectopic pregnancy. DESIGN: Retrospective cohort study. SETTING: Clinical University Center, Hvidovre Hospital, Copenhagen. POPULATION: Two hundred and seventy-six women undergoing salpingectomy or tubotomy for their first ectopic pregnancy between January 1992 and January 1999 and who actively attempted to conceive were followed for a minimum of 18 months. METHODS: Retrospective cohort study combined with questionnaire to compare reproductive outcome following salpingectomy or tubotomy for ectopic pregnancy. Cumulative probabilities of pregnancy for each group were calculated by the Kaplan-Meier estimator and compared by Cox regression analysis to control for potential confounders. MAIN OUTCOME MEASURES: Intrauterine pregnancy rates and recurrence rates of ectopic pregnancy after surgery for ectopic pregnancy. RESULTS: The cumulative intrauterine pregnancy rate was significantly higher after tubotomy (88%) than after salpingectomy (66%) (log rank P < 0.05) after correction for confounding factors. No difference was found in the recurrence rate of ectopic pregnancy between the treatments (16% vs 17%). In patients with contralateral tubal pathology, the chance of pregnancy was poor (hazard ratio 0.463) and the risk of recurrence was high (hazard ratio 2.25), assessed with Cox regression. The rate of persistent ectopic pregnancy was 8%. CONCLUSION: Conservative surgery is superior to radical surgery at preserving fertility. Conservative surgery is not followed by an increased risk of repeat ectopic pregnancy, but by the risk of persistent ectopic pregnancy, which should be taken into account when deciding on the operative procedure. Management in case of contralateral tubal pathology is disputed and should ideally be addressed in a randomised clinical trial.

Anaesthesia for minimally invasive gastric and bowel surgery.

It is of great importance that anaesthetic regimens match surgical procedures in regard to surgical time, in reducing organ dysfunction elicited by the anaesthesia and surgical trauma and by providing optimal post-operative pain treatment, leaving the possibility of early mobilization. New, rapidly eliminated anaesthetic drugs are, by virtue of their pharmacodynamic and pharmacokinetic profiles, optimal for use; combined with continuous thoracic epidurals with local anaesthetics and low-dose opioids, these drugs may permit reduction of various post-operative complications. Minimally invasive surgical techniques (e.g. laparoscopy) lead to serious anaesthesiological considerations concerning changes in haemodynamic and pulmonary parameters and intra-abdominal blood flow changes caused by increased intra-abdominal pressures. Few studies have evaluated whether these changes affect surgical outcome and whether or not different anaesthetic regimens influence relevant morbidity parameters. In future documentation it is important that controlled, well-designed clinical studies evaluate how the advantages from multimodal anaesthetic techniques improve relevant surgical outcome.

Persistent ectopic pregnancy after linear salpingotomy: a non-predictable complication to conservative surgery for tubal gestation.

BACKGROUND: The drawback of conservative surgery for ectopic pregnancy (EP) is the risk of persistent trophoblast. The purpose was to characterize patients who develop persistent ectopic pregnancy (PEP) after salpingotomy for EP and to assess prognostic factors. METHODS: The medical records of 417 patients treated by salpingotomy for EP were reviewed. Forty-eight (11.5%) patients were diagnosed with persistent EP. The data were analyzed using the Mann-Whitney U-test, Fischer's exact test or the chi2-test. RESULTS: Of 417 women, 48 (11,5%) were treated for PEP by either repeat surgery (n = 25) or methotrexate (n = 23). Oral methotrexate failed in 4/19 cases while intramuscular (i.m.) methotrexate was successful in 4/4 cases. Women treated for PEP had a higher preoperative and a slower postoperative decline of serum human chorionic gonadotropin (hCG). Both the preoperative and the early postoperative hCG levels had a low diagnostic sensitivity (0.38-0.66) and specificity (0.74-0.77) for predicting PEP. In multivariate logistic analysis, none of the following clinical variables were predictive of PEP: duration of surgery, laparoscopic approach, history of previous EP, history of previous lower abdominal surgery, ruptured EP, pelvic adhesions, absence of products of conception at microscopy and hemoperitoneum. CONCLUSIONS: Persistent ectopic pregnancy can neither be predicted from clinical variables nor from single measurements of hCG with an accuracy sufficient for clinical use.

Potenciales evocados y bloqueo neural / Evoked potencials and nerve block

Se analizan estudios recientes para investigar el valor de los potenciales evocados somatosensitivos, en la evaluación de diversos procedimientos de anestesia regional. Los datos hasta ahora disponibles sugieren que el bloqueo de la conducción nerviosa en las fibras rápidas es menor de lo que cabría esperar de acuerdo a la extensión cefálica de la analgesia al pinchazo en anestesia raquídea o epidural lumbar con bupivacaina. Las dosis convencionales de bupivacaina en anestesia epidural torácica no tienen virtualmente efecto sobre los potenciales evocados aunque se presente analgesia quirúrgica. La Morfina epidural no parece ser capaz de modular los potenciales evocados tempranos tras la estimulación eléctrica en las metámeras afectadas por el fármaco. La infiltración de troncos nerviosos periféricos con anestésicos locales es más efectiva que los demás procedimientos respecto a interrumpir la transmisión del estímulo en las vías exploradas por medio de potenciales evocados. Se necesita mayor caudal de investigaciones para evaluar el valor de esta técnica en el estudio de los bloqueos regionales, centrales y periféricos (AU)

Potenciales evocados y bloqueo neural / Evoked potencials and nerve block

Se analizan estudios recientes para investigar el valor de los potenciales evocados somatosensitivos, en la evaluación de diversos procedimientos de anestesia regional. Los datos hasta ahora disponibles sugieren que el bloqueo de la conducción nerviosa en las fibras rápidas es menor de lo que cabría esperar de acuerdo a la extensión cefálica de la analgesia al pinchazo en anestesia raquídea o epidural lumbar con bupivacaina. Las dosis convencionales de bupivacaina en anestesia epidural torácica no tienen virtualmente efecto sobre los potenciales evocados aunque se presente analgesia quirúrgica. La Morfina epidural no parece ser capaz de modular los potenciales evocados tempranos tras la estimulación eléctrica en las metámeras afectadas por el fármaco. La infiltración de troncos nerviosos periféricos con anestésicos locales es más efectiva que los demás procedimientos respecto a interrumpir la transmisión del estímulo en las vías exploradas por medio de potenciales evocados. Se necesita mayor caudal de investigaciones para evaluar el valor de esta técnica en el estudio de los bloqueos regionales, centrales y periféricos