Accuracy of aPTT monitoring in critically ill patients treated with unfractionated heparin.

INTRODUCTION: The anticoagulant effect of unfractionated heparin (UFH) is usually monitored by means of the activated partial thromboplastin time (aPTT). In critically ill patients, however, increased levels of acute phase proteins may decrease the accuracy of the aPTT, leading to inadequate UFH dosing. In these circumstances, the anti-Xa assay is recommended for monitoring. OBJECTIVE: We aimed to analyse the accuracy of the aPTT for the monitoring of UFH dosing in critically ill patients. METHODS: In critically ill patients treated with therapeutic doses of UFH, we compared aPTT levels with simultaneously measured anti-Xa levels as the gold standard. Sensitivity and specificity of the aPTT were determined for different cut-off points, receiver operating characteristic (ROC) curves were constructed and their areas under the curve (AUCs) were calculated. RESULTS: A total of 171 paired blood samples from 58 patients were analysed. Concordant aPTT and anti-Xa values were observed in 108 (63.2%) data pairs. In 33 data pairs (19.3%) the aPTT was discordantly high and in 30 data pairs (17.5%) discordantly low. The sensitivity of the aPTT in detecting UFH underdosing and overdosing was 0.63 and 0.37, respectively. When considering alternative thresholds, ROC curves for underdosing and overdosing had AUCs of 0.71 and 0.81, respectively. CONCLUSION: In this small cohort of critically ill patients, the aPTT was accurate in 63.2% of the blood samples. Its sensitivity to detect UFH underdosing and overdosing was low (0.63 and 0.37, respectively). We conclude that in critically ill patients, the aPTT is not accurate enough to detect UFH underdosing and overdosing.

Monitoring of unfractionated heparin in critically ill patients.

BACKGROUND: In critically ill patients, dosing of unfractionated heparin (UFH) is difficult due to unpredictable pharmacokinetics, which has an impact on the time to reach therapeutic anticoagulation. We evaluated the quality of UFH therapy in critically ill patients in terms of activated partial thromboplastin time (APTT) test values and time to therapeutic range. METHODS: Patients admitted to the Intensive Care Unit (ICU) and Medium Care Unit (MCU) were screened for intravenous UFH administration. Time to therapeutic range was categorised into 0-12, 13-24 and >24 hours. APTT results were classified into categories of subtherapeutic, supratherapeutic and therapeutic tests. We identified to what extent the sub- and upratherapeutic values were aberrant of the limit of the therapeutic range (15%). RESULTS: In 101 patients admitted to the ICU and MCU, time to therapeutic range was 24 hours in 56% of the population, whereas in 10% of the patients no therapeutic APTT was achieved during UFH treatment. Among the APTT levels, 29% of all test results measured in 24 hours were within the therapeutic range. Subtherapeutic values were found in 53% of the test results, of which 160/203 were more than 15% under the lower limit, whereas 18% of the test results were supratherapeutic, of which 40/69 more than 15% above the upper limit. CONCLUSION: In this cohort of critically ill patients, therapeutic APTT values were reached within 24 hours in 56% of the patients. We conclude that intravenous UFH therapy can be improved in critically ill patients.

Recovery from near drowning and postanoxic status epilepticus with controlled hypothermia.

A diver was resuscitated after cardiac arrest due to near drowning and was hypothermic on hospital arrival. During rewarming, status epilepticus occurred, previously identified as a predictor of poor outcome. The seizures responded well to treatment with antiepileptic drugs and controlled hypothermia. After six weeks, the patient had completely recovered. This case supports the hypothesis that hypothermia offers neuroprotection, even in the presence of status epilepticus. We recommend that near-drowning victims who are comatose after resuscitation for cardiac arrest be treated with controlled mild hypothermia for 12 to 24 hours.

[Induced mild hypothermia to limit neurological damage after resuscitation]. / Koeling ter beperking van neurologische schade na resuscitatie.

Despite improvements in resuscitation techniques, the prognosis for patients who experience cardiac arrest outside of a hospital remains relatively poor. This is mainly due to brain damage that occurs as a result of global cerebral ischaemia. In 2002, two prospective randomised multicentre studies demonstrated that induced mild hypothermia can increase the chance of good neurologic recovery after out-of-hospital cardiac arrest by at least 40%. For this reason, induced mild hypothermia (32-34 degrees C) was included in the resuscitation guidelines developed by the International Liaison Committee on Resuscitation. Mild hypothermia is relatively easy to apply and has few complications. Compared with normothermia, induced mild hypothermia increases the chance of good neurological recovery by 1.7-fold. A safe and effective method to induce mild hypothermia is the infusion of cold fluids during sedation and mechanical ventilation. Cardiac function, renal function and electrolytes must be monitored closely during induced mild hypothermia. Given the potentially deleterious effects of rapid rewarming, a maximal rewarming rate of 0.5 degrees C per hour is recommended.

[Pyelonephritis during pregnancy: a threat to mother and child]. / Pyelonefritis in de zwangerschap: een bedreiging voor moeder en kind.

Two pregnant women, aged 19 and 40 respectively, were diagnosed with pyelonephritis. The first patient was initially treated with amoxicillin; appropriate antibiotic treatment--consisting of amoxicillin and clavulanic acid--was delayed for 24 hours. The second patient immediately received appropriate treatment (ceftriaxone). The first patient eventually had a nephrostomy and died due to urosepsis with multiple organ failure. The second patient delivered a healthy son and recovered. Approximately 20% of the cases of pyelonephritis during pregnancy progress to urosepsis. Therefore, pregnant women with pyelonephritis should be treated immediately with an intravenous second- or third-generation cephalosporin or the combination ofamoxicillin and clavulanic acid. Treatment of pregnant patients with urosepsis should take place in an intensive care unit and include treatment of the underlying infection as well as support of vital functions. Nephrostomy in a pregnant patient with symptomatic hydronephrosis should only be performed when the symptoms persist despite adequate antibiotic treatment.

[Fatal autointoxication with metformin]. / Een fatale auto-intoxicatie met metformine.

A 39-year-old woman with type-2 diabetes mellitus presented with metabolic acidosis due to an attempted suicide with metformin. Despite treatment with activated charcoal and laxation, she experienced cardiac arrest, which required resuscitation. After transfer to another hospital, she was treated with high-volume continuous venovenous haemofiltration. However, she died due to multiple organ failure. Metformin is the most widely used oral antidiabetic agent in the world and the first-choice treatment for patients with type-2 diabetes mellitus. Metformin overdose can cause lactic acidosis, which usually manifests as abdominal pain, vomiting and diarrhoea. Although rare, metformin-associated lactic acidosis carries a high mortality risk. The treatment of choice is immediate haemodialysis and orally administered activated charcoal. If a patient treated with metformin presents with metabolic acidosis, lactic acidosis due to metformin overdose should be suspected and appropriate treatment should be initiated immediately.

[The guideline 'Treatment of acute carbon-monoxide poisoning' from doctors in clinics with a tank for hyperbaric ventilation]. / Richtlijn 'behandeling koolmonoxide-intoxicatie' van artsen uit klinieken met een hyperpressietank.

The guideline 'Treatment of acute carbon-monoxide poisoning' from doctors in clinics with a tank for hyperbaric ventilation Carbon-monoxide (CO) poisoning is a potentially life-threatening emergency. Its prognosis is determined by prompt recognition and treatment. CO is toxic because it binds to haemoglobin (Hb), thus impairing oxygen transport and causing tissue hypoxia. The most important symptoms are headache and altered consciousness, ranging from somnolence to coma. The diagnosis is based on a history ofCO exposure combined with an elevated carboxyhaemoglobin (HbCO) level in the blood. On the basis of the available literature, it is recommended that patients with a HbCO level > or = 10% should always be treated. In patients requiring artificial ventilation, 100% oxygen for 8 hours is recommended. In pregnant women and in patients who are or have been comatose, hyperbaric oxygen can be considered. In all other symptomatic patients, use of a non-rebreathing mask with 100% oxygen for 8 hours is recommended.

Anticoagulation strategies in continuous renal replacement therapy: can the choice be evidence based?

OBJECTIVES: Critical illness increases the tendency to both coagulation and bleeding, complicating anticoagulation for continuous renal replacement therapy (CRRT). We analyzed strategies for anticoagulation in CRRT concerning implementation, efficacy and safety to provide evidence-based recommendations for clinical practice. METHODS: We carried out a systematic review of the literature published before June 2005. Studies were rated at five levels to create recommendation grades from A to E, A being the highest. Grades are labeled with minus if the study design was limited by size or comparability of groups. Data extracted were those on implementation, efficacy (circuit survival), safety (bleeding) and monitoring of anticoagulation. RESULTS: Due to the quality of the studies recommendation grades are low. If bleeding risk is not increased, unfractionated heparin (activated partial thromboplastin time, APTT, 1-1.4 times normal) or low molecular weight heparin (anti-Xa 0.25-0.35 IU/l) are recommended (grade E). If facilities are adequate, regional anticoagulation with citrate may be preferred (grade C). If bleeding risk is increased, anticoagulation with citrate is recommended (grade D(-)). CRRT without anticoagulation can be considered when coagulopathy is present (grade D(-)). If clotting tendency is increased predilution or the addition of prostaglandins to heparin may be helpful (grade C(-)). CONCLUSION: Anticoagulation for CRRT must be tailored to patient characteristics and local facilities. The implementation of regional anticoagulation with citrate is worthwhile to reduce bleeding risk. Future trials should be randomized and should have sufficient power and well defined endpoints to compensate for the complexity of critical illness-related pro- and anticoagulant forces. An international consensus to define clinical endpoints is advocated.

Recombinant nematode anticoagulant protein c2, an inhibitor of tissue factor/factor VIIa, attenuates coagulation and the interleukin-10 response in human endotoxemia.

The tissue factor-factor (F)VIIa complex (TF/FVIIa) is responsible for the initiation of blood coagulation under both physiological and pathological conditions. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of TF/FVIIa, mechanistically distinct from tissue factor pathway inhibitor. The first aim of this study was to elucidate the pharmacokinetics and pharmacodynamics of a single intravenous (i.v.) dose of rNAPc2. The second aim was to study its effect on endotoxin-induced coagulation and inflammation. Initially, rNAPc2 was administered to healthy volunteers in three different doses. There were no safety concerns and the pharmacokinetics were consistent with previous studies, in which rNAPc2 was administered subcutaneously. rNAPc2 elicited a dose-dependent reduction of the endogenous thrombin potential and a selective prolongation of prothrombin time. Subsequently, the effect on endotoxin-induced coagulation and inflammation was studied. The administration of rNAPc2 completely blocked the endotoxin-induced thrombin generation, as measured by plasma prothrombin fragment F1+2. The endotoxin-induced effect on fibrinolytic parameters such as plasmin-antiplasmin complexes and plasminogen activator inhibitor type 1 was not affected by rNAPc2. The administration of rNAPc2 attenuated the endotoxin-induced rise in interleukin (IL)-10, without affecting the rise in other cytokines. In conclusion, rNAPc2 is a potent inhibitor of TF/FVIIa, which was well tolerated and could safely be used intravenously in this Phase I study in healthy male volunteers. A single i.v. dose rNAPc2 completely blocked endotoxin-induced thrombin generation without affecting the fibrinolytic response. In addition, rNAPc2 attenuated the endotoxin-induced rise in IL-10, without affecting the rises in other cytokines.