Low Incidence of Biphasic Allergic Reactions in Patients Admitted to Intensive Care after Anaphylaxis.

BACKGROUND: Biphasic allergic reactions-recurrence of allergy symptoms after a symptom-free period-are reported to occur in 1 to 23% of allergic reactions. Patients admitted to an intensive care unit after anaphylaxis potentially have more severe reactions and a higher risk of biphasic allergic reactions. The purpose of this study was to examine incidence, triggers, symptoms, and treatment of biphasic allergic reactions, in patients admitted to an intensive care unit. METHODS: Records of patients admitted to intensive care units with anaphylaxis from 2011 to 2014 were reviewed. Only patients with a reaction fulfilling internationally accepted criteria for anaphylaxis were included. Potential biphasic allergic reactions, defined as renewed allergy symptoms 1 to 72 h after initial symptoms had resolved, without further exposure to the trigger, were identified. RESULTS: A total of 83 cases of anaphylaxis were identified, and the most frequent triggers were medications (58 of 83 [70%]). Skin symptoms occurred in 69 (83%) cases, and circulatory and respiratory symptoms in 48 (58%) and 45 (54%) cases, respectively. In total, 82 (99%), 80 (96%), and 66 (80%) were treated with antihistamines, corticosteroids, and epinephrine, respectively. Only 10 patients presented with one or more relevant symptoms after the initial allergic reaction. Of these, three were possible, and one was a probable biphasic allergic reaction, giving a total incidence of 4 of 83 (4.8% [95% CI, 1.6 to 12.5]) or 1 of 83 (1.2% [95% CI, 0.1 to 7.46]), respectively. All cases were mild, presenting with skin symptoms only, occurring on average 14 h after initial reactions. CONCLUSIONS: The authors observed a low incidence of biphasic reactions in patients admitted to an intensive care unit after anaphylaxis, at a rate equivalent to that reported in other patient groups.

High-sensitivity detection of cardiac troponin I with UV LED excitation for use in point-of-care immunoassay.

High-sensitivity cardiac troponin assay development enables determination of biological variation in healthy populations, more accurate interpretation of clinical results and points towards earlier diagnosis and rule-out of acute myocardial infarction. In this paper, we report on preliminary tests of an immunoassay analyzer employing an optimized LED excitation to measure on a standard troponin I and a novel research high-sensitivity troponin I assay. The limit of detection is improved by factor of 5 for standard troponin I and by factor of 3 for a research high-sensitivity troponin I assay, compared to the flash lamp excitation. The obtained limit of detection was 0.22 ng/L measured on plasma with the research high-sensitivity troponin I assay and 1.9 ng/L measured on tris-saline-azide buffer containing bovine serum albumin with the standard troponin I assay. We discuss the optimization of time-resolved detection of lanthanide fluorescence based on the time constants of the system and analyze the background and noise sources in a heterogeneous fluoroimmunoassay. We determine the limiting factors and their impact on the measurement performance. The suggested model can be generally applied to fluoroimmunoassays employing the dry-cup concept.

Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients.

BACKGROUND: Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V1A-selective vasopressin analogue, was examined in a phase IIa trial in septic shock patients. METHODS: This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support) who received selepressin 1.25 ng/kg/minute (n = 10), 2.5 ng/kg/minute (n = 19), 3.75 ng/kg/minute (n = 2), or placebo (n = 21) until shock resolution or a maximum of 7 days. If mean arterial pressure (MAP) ≥65 mmHg was not maintained, open-label norepinephrine was added. Co-primary endpoints were maintenance of MAP >60 mmHg without norepinephrine, norepinephrine dose, and proportion of patients maintaining MAP >60 mmHg with or without norepinephrine over 7 days. Secondary endpoints included cumulative fluid balance, organ dysfunction, pharmacokinetics, and safety. RESULTS: A higher proportion of the patients receiving 2.5 ng/kg/minute selepressin maintained MAP >60 mmHg without norepinephrine (about 50% and 70% at 12 and 24 h, respectively) vs. 1.25 ng/kg/minute selepressin and placebo (p < 0.01). The 7-day cumulative doses of norepinephrine were 761, 659, and 249 µg/kg (placebo 1.25 ng/kg/minute and 2.5 ng/kg/minute, respectively; 2.5 ng/kg/minute vs. placebo; p < 0.01). Norepinephrine infusion was weaned more rapidly in selepressin 2.5 ng/kg/minute vs. placebo (0.04 vs. 0.18 µg/kg/minute at 24 h, p < 0.001), successfully maintaining target MAP and reducing norepinephrine dose vs. placebo (first 24 h, p < 0.001). Cumulative net fluid balance was lower from day 5 onward in the selepressin 2.5 ng/kg/minute group vs. placebo (p < 0.05). The selepressin 2.5 ng/kg/minute group had a greater proportion of days alive and free of ventilation vs. placebo (p < 0.02). Selepressin (2.5 ng/kg/minute) was well tolerated, with a similar frequency of treatment-emergent adverse events for selepressin 2.5 ng/kg/minute and placebo. Two patients were infused at 3.75 ng/kg/minute, one of whom had the study drug infusion discontinued for possible safety reasons, with subsequent discontinuation of this dose group. CONCLUSIONS: In septic shock patients, selepressin 2.5 ng/kg/minute was able to rapidly replace norepinephrine while maintaining adequate MAP, and it may improve fluid balance and shorten the time of mechanical ventilation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01000649 . Registered on September 30, 2009.

[Fatal succinylcholine-induced hyperkalemia in an intensive care unit]. / Fatal suxamethoniuminduceret hyperkaliæmi på intensivafdeling.

Succinylcholine-induced hyperkalemia is reported, but is still used in rapid sequence induction. In our case a 44 year-old man with septic shock was mechanically ventilated for 13 days, extubated but because of respiratory insufficiency reintubated. During induction an increase in p-potassium (4.2-11.7 mmol/l) caused ventricular fibrillation. Immobilization/infection cause an up-regulation and change in acetylcholine receptors is probably the reason for the extensive hyperkalemia and death. Caution in using succinylcholine is recommended and using rocuronium as an alternative is discussed.

[Survival following lightning strike and treatment of sequelae]. / Overlevelse efter lynnedslag og behandling af tilstødende komplikationer.

Lightning strike is an unpredictable weather phenomenon which can cause a variety of injuries to the human body. We present a case report with a 24-year-old male football player, who survived prolonged cardiac arrest after a lighting strike and then presented with multiple organ dysfunction due to cellular swelling, extreme rhabdomyolysis and global hypoperfusion. We describe the clinical observations, therapy and injuries which may be expected. Furthermore, the pathophysiology and factors influencing the survival of this patient are discussed.

[Mild therapeutic hypothermia after cardiac arrest through continuous dialysis]. / Mild terapeutisk hypotermi efter hjertestop ved hjaelp af kontinuerlig dialyse.

INTRODUCTION: Mild therapeutic hypothermia (32-34 degrees C) after resuscitation from cardiac arrest to protect the brain against global ischaemia was first described in two independent randomized controlled studies in 2002. This manuscript describes a method to induce and maintain a target temperature of 32-33 degrees C after cardiac arrest for 24 hours with continuous renal replacement therapy (CRRT). MATERIAL AND METHODS: Intravenous infusion of 30 ml/kg of normal saline 4 degrees C over 30 minutes was immediately started if such treatment had not been initiated upon arrival to the unit. Continuous venovenous haemofiltration (CVVH) was initiated and mild therapeutic hypothermia was maintained for 24 hours. The patient's core temperature was subsequently increased at a rate of 0.5-1.0 degrees C per hour. RESULTS: Over a two-year period, 33 patients were treated with mild therapeutic hypothermia. The median time from the patient's arrival to the intensive care unit and the achievement of a temperature between 32 degrees C and 34 degrees C was 4.2 hours, and the time to established CRRT was 1.7 hours. The median temperature during the treatment was 33.2 degrees C, and it was maintained for a median period of 24.5 hours. Passive rewarming had a median duration of 5 hours. The only complication was bradycardia which did not cause treatment changes. Eleven (39%) patients had a favorable neurological outcome. CONCLUSION: The described CRRT cooling method is a useful method for reaching and maintaining the target temperature. The method is especially suitably for intensive care units that use CRRT on a daily basis for patients with acute renal failure.

The Procalcitonin And Survival Study (PASS) - a randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients.

BACKGROUND: Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients. METHODS: Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age > or = 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent.Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. DISCUSSION: For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number at clinicaltrials.gov: Id. nr.: NCT00271752).

Pain treatment on outpatient basis utilizing extradural opiates. A Danish multicentre study comprising 105 patients.

Previous to October 1st, 1981, 8 major Danish anaesthesiological departments registered 105 patients treated with extradural opiates for a period of more than 7 days, partially or completely on outpatient basis. Ninety-four suffered from painful malignant diseases and 11 patients from various painful benign diseases. The mean period of treatment was 65 days (range: 7-283 days) and of these 49 days (2-266 days) as outpatients. The total number of inserted epidural catheters was 215, equivalent of an average of 2 per patient (range 1-5). Reasons for removing an extradural catheter were injection-related pain, difficulty in injecting the desired volume, and displacement of catheter. Morphine chloride, in a solution of 0.4 mg/ml of normal saline, was the main choice as analgesic agent (90 patients). The mean daily dose of this drug totalled 12.6 +/- 4.8 mg (S.D.) (range: 4-30 mg) distributed as 2.7 +/- 0.9 (S.D.) (range: 1-6) daily injections. Twelve patients were treated with buprenorphine extradurally. Satisfactory pain relief was achieved for 70 patients (67%) who managed with extradural opiates as sole analgesic treatment. One patient developed septicaemia with a non-fatal outcome probably originating from some other focus. Apart from this no serious side effects were reported. Medically unskilled persons or relatives were responsible for instillation of all extradural opiates with 42 patients and partially responsible with 14 patients. Eleven patients managed injections without assistance. District nurses took care of medication for 46 patients, aided by a general practitioner in 5 cases. Three patients were supplied with continuous extradural infusion by means of a Mill Hill microinfusion pump.