Anne Berit Guttormsen

Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis.

BACKGROUND Hydroxyethyl starch (HES) [corrected] is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringers acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringers acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringers acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringers acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.).

Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock

BACKGROUND Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization. RESULTS We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups. CONCLUSIONS Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).

Scandinavian Clinical Practice Guidelines on the diagnosis, management and follow-up of anaphylaxis during anaesthesia*

The present approach to the diagnosis, management and follow‐up of anaphylaxis during anaesthesia varies in the Scandinavian countries. The main purpose of these Scandinavian Clinical Practice Guidelines is to increase the awareness about anaphylaxis during anaesthesia amongst anaesthesiologists. It is hoped that increased focus on the subject will lead to prompt diagnosis, rapid and correct treatment, and standardised management of patients with anaphylactic reactions during anaesthesia across Scandinavia.

Anaphylaxis during anesthesia in Norway: a 6-year single-center follow-up study.

Background: Several studies have recognized neuromuscular blocking agents as the most common cause of anaphylaxis during general anesthesia, but the reported frequencies vary considerably between countries. In Norway, the issue has raised special concern because of reports from the Norwegian Medicines Agency that suggest a high prevalence. This article presents the results from a standardized allergy follow-up examination of 83 anaphylactic reactions related to general anesthesia performed at one allergy center in Bergen, Norway. Methods: Eighty-three cases were examined during the 6-yr period of 1996–2001. The diagnostic protocol consisted of case history, serum tryptase measurements, specific immunoassays, and skin tests. Results: Immunoglobulin E–mediated anaphylaxis was established in 71.1% of the cases, and neuromuscular blocking agents were by far the most frequent allergen (93.2%). Suxamethonium was the most frequently involved substance, followed by rocuronium and vecuronium. The few reactions in which other allergies could be detected were mainly linked to latex (3.6%). Conclusions: Neuromuscular blocking agents were the dominating antigens causing immunoglobulin E–mediated anaphylaxis in this study. The data could not be used for estimation of the incidence of allergy toward neuromuscular blocking agents in Norway. Larger patient samples, standardization of reporting, and diagnostic protocols should be pursued by network formation to produce data more suitable for epidemiologic research.

Assessment of homocysteine status

Plasma total homocysteine (tHcy) determination is used in the diagnosis of homocystinuria, in cobalamin and folate deficiency and in cardiovascular risk assessment. However, determination of tHcy includes many pitfalls which complicate the assessment of homocysteine status. In the present article, we review basic knowledge for a rational use of plasma tHcy in diagnostic as well as scientific work. The subjects dealt with are procedures for sample handling and processing, the principles of tHcy analyses, and genetic and acquired determinants of the plasma tHcy concentration.

Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients.

Background: Low plasma glutamine concentration is an independent prognostic factor for an unfavourable outcome in the intensive care unit (ICU). Intravenous (i.v.) supplementation with glutamine is reported to improve outcome. In a multi‐centric, double‐blinded, controlled, randomised, pragmatic clinical trial of i.v. glutamine supplementation for ICU patients, we investigated outcomes regarding sequential organ failure assessment (SOFA) scores and mortality. The hypothesis was that the change in the SOFA score would be improved by glutamine supplementation.

Monitoring cobalamin inactivation during nitrous oxide anesthesia by determination of homocysteine and folate in plasma and urine

The effects of nitrous oxide‐induced cobalamin inactivation on homocysteine and folate metabolism have been investigated. Plasma levels of cobalamin, folate, homocysteine, and methionine were determined in 40 patients before and after operation under nitrous oxide anesthesia (range of exposure time, 70 to 720 minutes). Twelve patients anesthetized with total intravenous anesthesia served as control subjects (range of exposure time, 115 to 600 minutes). Postoperative plasma levels of folate and homocysteine increased (p < 0.001) up to 220% and 310%, respectively, in nitrous oxide‐exposed patients, whereas plasma levels of methionine decreased (p < 0.025). Response occurred after 75 minutes of nitrous oxide exposure. The percentage increase of plasma folate and homocysteine correlated significantly with exposure time (p < 0.025 and p < 0.0001, respectively). In eight patients receiving nitrous oxide anesthesia plasma homocysteine levels had not returned to preoperative levels within 1 week (p < 0.01). Urinary excretion of folate and homocysteine increased during and after nitrous oxide exposure (p < 0.01 and p < 0.002, respectively) and correlated with exposure time (p < 0.01 and p < 0.005, respectively). It can be concluded that disturbance of homocysteine and folate metabolism by nitrous oxide develops with little delay and return to normal levels requires several days. Elevation of plasma homocysteine levels may therefore be used for monitoring nitrous oxide‐induced cobalamin inactivation.

Anaphylactic reactions during induction of anaesthesia using rocuronium for muscle relaxation: A report including 3 cases

Anaphylaxis during induction of anaesthesia is a dreaded complication with a mortality rate of 3–6%, most frequently associated with the use of muscle relaxants. Current knowledge on this matter is reviewed in relation to the presentation of 3 cases of anaphylaxis and bronchospasm associated with the use of the recently released nondepolarizing muscle relaxant rocuronium. Bronchospasm may be the sole sign of a serious drug reaction, triggered by precipitation of insoluble thiopental crystals when mixed with a muscle relaxant in the intravenous (iv) line. It is recommended that these drugs are administered via different injection ports. The hypotension requires immediate treatment with oxygen, epinephrine and large amounts of iv fluids. Epinephrine infusion may be needed for hours. It is recommended that serum tryptase is measured approximately 2 h after debut of the serious drug reaction. Allergy testing should be performed for all the drugs the patient was exposed to, 4–8 weeks after the incident, and due to cross‐reactivity, including all available muscle relaxants. Doctors are urged to inform their patients, and systematically register adverse drug reactions.

National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study

To cite this article: Johansson SGO, Florvaag E, Öman H, Poulsen LK, Mertes PM, Harper NJN, Garvey LH, Gerth van Wijk R, Metso T, Irgens A, Dybendal T, Halsey J, Seneviratne SL, Guttormsen AB. National pholcodine consumption and prevalence of IgE‐sensitization: a multicentre study. Allergy 2010; 65: 498–502.

Screening for mast cell tryptase and serum IgE antibodies in 18 patients with anaphylactic shock during general anaesthesia

Background:  In the perioperative setting multiple agents can cause anaphylaxis. Often the reactions are dramatic, and due to their lifethreatening potential it is crucial that the responsible agent is identified in order to avoid future adverse reactions. The aim of the present study was to measure the concentration of serum mast cell tryptase (MCT), to investigate the prevalence of serum IgE antibodies against ammonium groups, choline, morphine, suxamethonium, thiopentone and latex and to perform skin prick tests (SPTs) in 18 patients experiencing an anaphylactic reaction during induction of general anaesthesia.