Disseminated intravascular coagulation in cardiac arrest and resuscitation

The aims of this review are to demonstrate that the changes in coagulation and fibrinolysis observed in cardiac arrest and resuscitation can be recognized as disseminated intravascular coagulation (DIC), and to discuss the probability of DIC being a therapeutic target. The appearance of triggers of DIC, such as damage‐associated molecular patterns, inflammatory cytokines, and adrenaline, is associated with platelet activation, marked thrombin generation and fibrin formation, insufficient anticoagulation pathways, and increased fibrinolysis by tissue‐type plasminogen activator, followed by the suppression of fibrinolysis by plasminogen activator inhibitor‐1, in patients with cardiac arrest and resuscitation. Simultaneous neutrophil activation and endothelial injury associated with glycocalyx perturbation have been observed in these patients. The degree of these changes is more severe in patients with prolonged precardiac arrest hypoxia and long no‐flow and low‐flow times, patients without return of spontaneous circulation, and non‐survivors. Animal and clinical studies have confirmed decreased cerebral blood flow and microvascular fibrin thrombosis in vital organs, including the brain. The clinical diagnosis of DIC in patients with cardiac arrest and resuscitation is associated with multiple organ dysfunction, as assessed with the sequential organ failure assessment score, and increased mortality. This review confirms that the coagulofibrinolytic changes in cardiac arrest and resuscitation meet the definition of DIC proposed by the ISTH, and that DIC is associated with organ dysfunction and poor patient outcomes. This evidence implies that established DIC should be considered to be one of the main therapeutic targets in post–cardiac arrest syndrome.     

Disseminated intravascular coagulation score is associated with mortality for children with shock

Objective  To evaluate the association between disseminated intravascular coagulation (DIC) score and mortality for children with shock. Design  Retrospective. Setting  Tertiary care, 20-bed pediatric intensive care unit. Patients  A total of 132 children with sepsis or shock admitted from January 2003 to December 2005. Measurements and results  A total of 132 patients less than 18 years of age with a diagnosis of shock or sepsis were included in the analysis. Of these patients, 90 survived and 42 died (31.8%). Patients ranged from 6 days to 18 years (median 5.8 years), and were a majority male (63%). Variables associated with mortality included peak DIC score within 24 h of ICU admission, age, weight, volume of blood products transfused, inotrope score, pediatric index of mortality (PIM 2) score, 12-h pediatric risk of mortality (PRISM III) score and presence of mechanical ventilation (P < 0.05). Patients with DIC scores ≥ 5 (overt DIC) had 50% mortality, compared to 20% for patients with DIC scores < 5. Overall, a one-point rise in DIC score was associated with an increased risk of mortality after adjusting for age, race, gender, hemodynamic instability, and PRISM III score [OR 1.35 (1.02, 1.78)]. Most patients achieve their peak DIC score within 2 h of ICU admission. Conclusions  This analysis suggests that DIC score, easily calculated early in ICU admission, is associated with mortality for children with sepsis and shock, regardless of initial severity of illness or inotrope use.     

The occurrence of shivering in cardiac arrest survivors undergoing therapeutic hypothermia is associated with a good neurologic outcome

Background

The incidence of shivering in cardiac arrest survivors who undergo therapeutic hypothermia (TH) is varied. Its occurrence is dependent on the integrity of multiple peripheral and central neurologic pathways. We hypothesized that cardiac arrest survivors who develop shivering while undergoing TH are more likely to have intact central neurologic pathways and thus have better neurologic outcome as compared to those who do not develop shivering during TH.

Methods

Prospectively collected data on consecutive adult patients admitted to a tertiary center from 1/1/2007 to 11/1/2010 that survived a cardiac arrest and underwent TH were retrospectively analyzed. Patients who developed shivering during the cooling phase of TH formed the “shivering” group and those that did not formed the “non-shivering” group. The primary end-point: Pittsburgh Cerebral Performance Category (CPC) scale; good (CPC 1–2) or poor (CPC 3–5) neurological outcome prior to discharge from hospital.

Results

Of the 129 cardiac arrest survivors who underwent TH, 34/94 (36%) patients in the “non-shivering” group as compared to 21/35 (60%) patients in the “shivering” group had good neurologic outcome (P = 0.02). After adjusting for confounders using binary logistic regression, occurrence of shivering (OR: 2.71, 95% CI 1.099–7.41, P = 0.04), time to return of spontaneous circulation (OR: 0.96, 95% CI 0.93–0.98, P = 0.004) and initial presenting rhythm (OR: 4.0, 95% CI 1.63–10.0, P = 0.002) were independent predictors of neurologic outcome.

Conclusion

The occurrence of shivering in cardiac arrest survivors who undergo TH is associated with an increased likelihood of good neurologic outcome as compared to its absence.     

Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms

Aim

Mild therapeutic hypothermia (32-34 °C) improves neurological recovery and reduces the risk of death in comatose survivors of cardiac arrest when the initial rhythm is ventricular fibrillation or pulseless ventricular tachycardia. The aim of the presented study was to investigate the effect of mild therapeutic hypothermia (32-34 °C for 24 h) on neurological outcome and mortality in patients who had been successfully resuscitated from non-ventricular fibrillation cardiac arrest.

Methods

In this retrospective cohort study we included cardiac arrest survivors of 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest with asystole or pulseless electric activity as the first documented rhythm. Data were collected from 1992 to 2009. Main outcome measures were neurological outcome within six month and mortality after six months.

Results

Three hundred and seventy-four patients were analysed. Hypothermia was induced in 135 patients. Patients who were treated with mild therapeutic hypothermia were more likely to have good neurological outcomes in comparison to patients who were not treated with hypothermia with an odds ratio of 1.84 (95% confidence interval: 1.08-3.13). In addition, the rate of mortality was significantly lower in the hypothermia group (odds ratio: 0.56; 95% confidence interval: 0.34-0.93).

Conclusion

Treatment with mild therapeutic hypothermia at a temperature of 32-34 °C for 24 h is associated with improved neurological outcome and a reduced risk of death following out-of-hospital cardiac arrest with non-shockable rhythms.     

盲肠结扎穿孔建立小鼠弥漫性血管内凝血动物模型的研究

目的应用盲肠结扎穿孔术(CLP)建立小鼠弥漫性血管内凝血(DIC)动物模型。方法将昆明小鼠随机分为假手术组(sham)、中度CLP组(mCLP)和重度CLP组(hCLP),检测术后即刻、2、6、12、24、48、72 h共7个时间点的外周血血小板计数(PLT)、谷丙转氨酶(ALT)、肌酐(Cr)、凝血酶原时间(PT)、部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、D-二聚体,计算72 h各组存活率,并进行组织病理切片观察。结果术后72 h小鼠sham组存活率均为100%,mCLP组存活率为60%,hCLP组存活率为10%(P<0.05)。与sham组相比,mCLP和hCLP组小鼠CLP术后6 h PLT、FIB明显下降,APTT+PT延长,D-二聚体、ALT升高,术后12 h Cr升高(P均<0.05),组织病理显示肺和肠系膜出现不同程度的微血栓形成。结论 CLP小鼠模型能够体现类似临床的DIC的发展过程,重度CLP小鼠模型可作为脓毒症性DIC研究的动物模型。     

Disseminated intravascular coagulation and acute myocardial necrosis caused by lightning

A 24-year-old woman was struck by lightning and suffered 20% second degree burns. She was admitted after cardiac and respiratory arrest. Despite intensive supportive care she died 24 h later of cardiogenic shock complicated by disseminated intravascular coagulation. At autopsy there was myocardial necrosis. Disseminated intravascular coagulation and myocardial necrosis are only rarely described as complications of lightning.     

急性白血病合并弥散性血管内凝血41例

目的探讨急性白血病（AL）合并弥散性血管内凝血（DIC）的临床特点及诊治经验。方法回顾性分忻41例AL合并DIC患者的临床资料,包括：白血病分型、临床症状、DIC发生的时间、实验室检查的相关结果及疗效等。结果AL尤其是急性早幼粒细胞白血病合并DIC 90％发生在白血病治疗前,肝素治疗AL合并DIC总有效率为75．6％,低分子肝素与小剂量普通肝素的疗效相同。结论急性早幼粒细胞白血病合并DIC防治的重点是在初发期;出血尤其是颅内出血是AL合并DIC死亡的重要原因;积极治疗原发疾病,有效的抗凝治疗及补充凝血因子是治疗成功的关键。     

Disseminated intravascular coagulation as the laboratory hallmark of acute Q fever

A 37-y-old white male presented with high fever, constitutional symptoms, mild meningeal and pulmonary involvement. Laboratory investigation revealed thrombocytopenia and excessive prolongation of coagulation times (International normalized ratio-INR- up to 6) requiring transfusion with 14 units of fresh frozen plasma. Serology established acute Coxiella burnetti infection. Patient recovered on levofloxacin.     

Modified score for disseminated intravascular coagulation in the critically ill

Objective To assess the value of the diagnosis of overt disseminated intravascular coagulation (DIC) according to the International Society on Thrombosis and Haemostasis (ISTH) criteria and that of the parameters included in the ISTH score for overt DIC in predicting day 28 mortality in intensive care patients. Also, to assess the value of the components of the score in the diagnosis of overt DIC.Design and setting Retrospective clinical study in a university hospital intensive care unit.Patients and participants 494 consecutive patients admitted in the ICU between January 2002 and October 2003.Measurements and results Clinical and laboratory data, including hemostatic parameters, were collected from computerized databases and patient files. Altogether 19% (95/494) of the patients fulfilled the criteria for overt DIC. Their day 28 mortality rate was higher than that of patients without overt DIC (40% vs. 16%). The lowest platelet count (area under curve, AUC, 0.910), highest plasma D-dimer (AUC 0.846), lowest antithrombin (AUC 0.823), and Owren-type prothrombin time activity (AUC 0.797) discriminated well the patients with and without overt DIC, whereas plasma fibrinogen (AUC 0.690) had poor discriminative power. No patient with the diagnosis of overt DIC had decreased plasma fibrinogen. Day-1 SOFA and APACHE II score, the first CRP measurement, and the lowest antithrombin were independent predictors of day 28 mortality.Conclusions The diagnosis of overt DIC was not an independent predictor of day 28 mortality. In ICU patients plasma antithrombin seems a promising candidate in the panel of indicators for overt DIC whereas the value of plasma fibrinogen is in doubt.     

Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI

Aim

To determine if early cardiac catheterization (CC) is associated with improved survival in comatose patients who are resuscitated after cardiac arrest when electrocardiographic evidence of ST-elevation myocardial infarction (STEMI) is absent.

Methods

We conducted a retrospective observational study of a prospective cohort of 754 consecutive comatose patients treated with therapeutic hypothermia (TH) following cardiac arrest.

Results

A total of 269 (35.7%) patients had cardiac arrest due to a ventricular arrhythmia without STEMI and were treated with TH. Of these, 122 (45.4%) received CC while comatose (early CC). Acute coronary occlusion was discovered in 26.6% of patients treated with early CC compared to 29.3% of patients treated with late CC (p = 0.381). Patients treated with early CC were more likely to survive to hospital discharge compared to those not treated with CC (65.6% vs. 48.6%; p = 0.017). In a multivariate regression model that included study site, age, bystander CPR, shock on admission, comorbid medical conditions, witnessed arrest, and time to return of spontaneous circulation, early CC was independently associated with a significant reduction in the risk of death (OR 0.35, 95% CI 0.18–0.70, p = 0.003).

Conclusions

In comatose survivors of cardiac arrest without STEMI who are treated with TH, early CC is associated with significantly decreased mortality. The incidence of acute coronary occlusion is high, even when STEMI is not present on the postresuscitation electrocardiogram.     

Beneficial effect of low-molecular-weight heparin against lipopolysaccharide-induced disseminated intravascular coagulation in rats is abolished by coadministration of tranexamic acid

Objective We examined the role of coagulation and fibrinolysis in lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in rats, studying their contribution to fibrin deposition and organ failure in rats with LPS-induced DIC by concurrent administration of low molecular weight heparin (LMWH) with or without tranexamic acid (TA).Methods DIC was induced in male Wistar rats by a 4-h infusion of LPS (30 mg/kg) via the tail vein (LPS group). In the LPS+LMWH group LMWH (200u/kg) was administered to rats from 30 min before the infusion of LPS for 4.5 h. In the LPS+LMWH+TA group LMWH (200 µg/kg) and TA (50 mg/kg) were administered to rats from 30 min before the infusion of LPS for 4.5 h.Results In the LPS+LMWH group lower plasma levels of TAT, D dimer, creatinine, and alanine aminotransferase were observed, along with less glomerular fibrin deposition and improved survival over rats administered LPS alone. However, these effects of LMWH were completely eliminated and damage beyond that observed in rats administered LPS alone resulted from combined administration of TA (LPS+LMWH+TA group), except that TAT and D dimer levels remained lower than in the group administered LPS alone.Conclusions Suppression of fibrinolysis by TA (despite coadministration of LMWH) resulted in increased organ damage in this study, suggesting that depressed fibrinolysis plays a large role in organ failure resulting from LPS-induced DIC, even though hemostatic activation is moderately suppressed by LMWH     

产科弥散性血管内凝血患者凝血指标动态观察及意义

目的探讨凝血实验室指标在产科弥散性血管内凝血(DIC)中的动态变化及临床意义。方法检测26例在分娩前后出现DIC的产妇,于确诊DIC时,对症治疗后2 h、24 h、7 d常规凝血试验及凝血因子Ⅷ促凝活性(Ⅷ∶C)、血浆D-二聚体(DD)、血管性血友病因子(VWF)、抗凝血酶活性(AT∶A)、纤溶酶原活性(PLG∶A)、凝血酶-抗凝血酶复合物(TAT)和组织因子(TF)含量,同时检测31名正常产妇作为对照。结果发生DIC的产妇治疗前与对照组比较,常规凝血试验均发生明显变化,治疗后各参数逐渐恢复正常,至第7天大部分参数在正常参考范围内;治疗前血浆DD、Ⅷ∶C、VWF、TF、TAT均明显高于对照组(P<0.01),AT∶A、PLG∶A均明显低于对照组(P<0.01),治疗后各参数均有不同程度的改善,第7天时,除DD、VWF、TF、PLG∶A有轻度异常外,其余参数基本正常。结论常规凝血指标及凝血分子标志物不仅可用于诊断产妇DIC,也是产妇DIC治疗过程中很好的监测指标。     

产科早期弥漫性血管内凝血患者止凝血功能的研究

目的研究正常孕妇不同孕期和产科早期弥漫性血管内凝血(DIC)患者的凝血、抗凝、纤溶和血管内皮系统的功能,了解所用分子标志物在早期诊断产科DIC中的价值和意义。方法检测了31例早孕、14例中孕、62例晚孕、34例产科早期DIC和31名正常对照的常规止凝血功能指标凝血酶原时间(PT)、部分凝血活酶时间(APTT)、纤维蛋白原(Fbg)、血小板(PLT)和分子标志物凝血酶原片段(F1+2)、凝血酶-抗凝血酶Ⅲ复合物(TAT)、纤维蛋白单体(FM)、血栓调节蛋白(TM)和D-二聚体(D-dimer)。结果PT、APTT在各实验组间差异无统计学意义(P>0·05),早期DIC组PLT(155±60)×109/L低于对照组(241±63)×109/L和妊娠各期组[分别为早孕组(233±64)×109/L、中孕组(203±50)×109/L、晚孕组(216±55)×109/L](P<0·05),Fbg、F1+2、TAT、FM、TM、D-dimer随着妊娠时间的延长浓度逐渐升高(P<0·05),早期DIC组Fbg(4·0±1·0)g/L与中孕组(3·8±0·8)g/L、晚孕组(4·1±0·5)g/L相比差异无统计学意义(P>0·05),早期DIC组TAT7·40(14·01)μg/L与中孕组6·41(5·51)μg/L、晚孕组8·58(5·84)μg/L相比差异无统计学意义(P>0·05)。早期DIC组F1+2(4·43±1·43)nmol/L、TM(31·5±8·5)μg/L、FM(43·7±16·8)mg/L、D-dimer(630±479)μg/L浓度显著升高,明显高于对照组和妊娠各期组(P<0·05)。除PLT和Fbg之间不存在直线相关关系外,指标F1+2、TAT、FM、TM、D-dimer、PLT、Fbg间均存在直线相关关系或等级相关关系(P<0·05)。结论TAT、Fbg可反映机体高凝状态,但不能早期诊断产科DIC。F1+2、FM、TM、D-dimer可作为早期诊断产科DIC的敏感指标。     

Therapeutic hypothermia is associated with improved neurologic outcome and survival in cardiac arrest survivors of non-shockable rhythms

Background

Therapeutic hypothermia improves neurologic outcomes in patients resuscitated from cardiac arrest due to ventricular fibrillation. However, its role in patients with cardiac arrest due to non-shockable rhythms (pulseless electrical activity (PEA) and asystole) is unclear. We hypothesized that therapeutic hypothermia favorably impacts neurologic outcome and survival in patients resuscitated from cardiac arrest due to non-shockable rhythms.

Methods

Retrospectively collected data on consecutive adult patients admitted to Hartford Hospital from 1/1/2004 to 11/1/2010 who survived a cardiac arrest due to PEA or asystole were analyzed. Patients who underwent therapeutic hypothermia (1/1/2007-11/1/2010) formed the hypothermia group while patients admitted prior to the institution of therapeutic hypothermia (1/1/2004-1/1/2007) at Hartford Hospital formed the control group. The primary end-point was measured using the Pittsburgh cerebral performance category (CPC) scale and patients were assessed for a good (CPC 1 and 2) or poor (CPC 3-5) neurological outcome prior to discharge from hospital. A secondary end-point was measured as survival at discharge from hospital.

Results

Of 100 post-cardiac arrest patients included in the study, 15/52 (29%) patients in the hypothermia group had a good neurologic outcome as compared to 5/43 (10%) patients in the control group (P = 0.021). On multivariate analysis, the odds ratio for good neurologic outcome and survival at discharge from the hospital with therapeutic hypothermia as compared to control were 4.35 (95% CI 1.10-17.24, P = 0.04) and 5.65 (CI 1.66-19.23, P = 0.006) respectively.

Conclusion

Therapeutic hypothermia is associated with favorable neurologic outcome and survival in patients resuscitated after cardiac arrest due to non-shockable rhythms.     

急性白血病并发弥散性血管内凝血前相关因素及其临床意义

目的探讨急性白血病并发弥散性血管内凝血(DIC)前的相关因素,以便早期诊断和积极预防DIC的发生。方法回顾性分析383例急性白血病患者的临床资料,其中确诊并发DIC46例,将确诊DIC前3~5d可能相关的17个因素与未发生DIC患者比较。结果外周血白细胞计数、M3在两组中所在比例差异显著(P<0.01),D二聚体含量、血浆组织因子、凝血酶抗凝血酶复合物、纤溶酶抗纤溶酶复合物、凝血酶原时间、活化部分凝血活酶时间6个因素两组间有显著差异(P<0.05)。血红蛋白、血小板、血脂、血糖、肌酐、血清乳酸脱氢酶及年龄、性别和体温等因素两组间无显著性差异。结论对白细胞计数升高及D二聚体、血浆组织因子、凝血酶抗凝血酶复合物、纤溶酶抗纤溶酶复合物水平高,凝血酶原时间、活化部分凝血活酶时间缩短以及急性早幼粒细胞白血病等(M3)患者应注意弥散性血管内凝血的发生。     

The association of body mass index with outcomes and targeted temperature management practice in cardiac arrest survivors

Purpose

Obesity is a well-known risk factor in various health conditions. We analyzed the association between obesity and clinical outcomes, and its effect on targeted temperature management (TTM) practice for cardiac arrest survivors by calculating and classifying their body mass indexes (BMIs).

Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: A systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia

Aims and methods

To systematically review the accuracy of early (≤7 days) predictors of poor outcome, defined as death or vegetative state (Cerebral Performance Categories [CPC] 4–5) or death, vegetative state or severe disability (CPC 3–5), in comatose adult survivors from cardiac arrest (CA) treated using therapeutic hypothermia (TH). Electronic databases were searched for eligible studies. Sensitivity, specificity, and false positive rates (FPR) for each predictor were calculated. Quality of evidence (QOE) was evaluated according to the GRADE guidelines.

Results

37 studies (2403 patients) were included. A bilaterally absent N20 SSEP wave during TH (4 studies; QOE: Moderate) or after rewarming (5 studies; QOE: Low), a nonreactive EEG background (3 studies; QOE: Low) after rewarming, a combination of absent pupillary light and corneal reflexes plus a motor response no better than extension (M ≤ 2) (1 study; QOE: Very low) after rewarming predicted CPC 3–5 with 0% FPR and narrow (<10%) 95% confidence intervals. No consistent threshold for 0% FPR could be identified for blood levels of biomarkers. In 6/8 studies on SSEP, in 1/3 studies on EEG reactivity and in the single study on clinical examination the investigated predictor was used for decisions to withdraw treatment, causing the risk of a self-fulfilling prophecy.

Conclusions

in the first 7 days after CA, a bilaterally absent N20 SSEP wave anytime, a nonreactive EEG after rewarming or a combination of absent ocular reflexes and M ≤ 2 after rewarming predicted CPC 3–5 with 0% FPR and narrow 95% CIs, but with a high risk of bias.     

Hyperfibrinolysis in out of hospital cardiac arrest is associated with markers of hypoperfusion

Aim of the study

This study investigated the incidence of hyperfibrinolysis upon emergency department (ED) admission in patients with out of hospital cardiac arrest (OHCA), and the association of the degree of hyperfibrinolysis with markers of hypoperfusion.

Methods

From 30 OHCA patients, cardiopulmonary resuscitation (CPR) time, pH, base excess (BE), and serum lactate were measured upon ED admission. A 20% decrease of rotational thromboelastometry maximum clot firmness (MCF) was defined as hyperfibrinolysis. Lysis parameters included maximum lysis (ML), lysis onset time (LOT) and lysis index at 30 and 45 min (LI30/LI45). The study was approved by the Human Subjects Committee.

Results

Hyperfibrinolysis was present in 53% of patients. Patients with hyperfibrinolysis had longer median CPR times (36 (15–55) vs. 10 (7–18) min; P = 0.001), a prolonged activated partial thromboplastin time (54 ± 16 vs. 38 ± 10 s; P = 0.006) and elevated D-dimers (6.1 ± 2.1 vs. 2.3 ± 2.0 μg/ml; P = 0.02) when compared to patients without hyperfibrinolysis. Hypoperfusion markers, including pH (6.96 ± 0.11 vs. 7.17 ± 0.15; P < 0.001), base excess (−20.01 ± 3.53 vs. −11.91 ± 6.44; P < 0.001) and lactate (13.1 ± 3.7 vs. 8.0 ± 3.7 mmol/l) were more disturbed in patients with hyperfibrinolysis than in non-hyperfibrinolytic subjects, respectively. The LOT showed a good association with CPR time (r = −0.76; P = 0.003) and lactate (r = −0.68; P = 0.01), and was longer in survivors (3222 ± 34 s) than in non-survivors (1356 ± 833; P = 0.044).

Conclusion

A substantial part of OHCA patients develop hyperfibrinolysis in association with markers for hypoperfusion. Our data further suggest that the time to the onset of clot lysis may be an important marker for the severity of hyperfibrinolysis and patient outcome.     

Intra-arrest cooling with delayed reperfusion yields higher survival than earlier normothermic resuscitation in a mouse model of cardiac arrest

BACKGROUND: Therapeutic hypothermia (TH) represents an important method to attenuate post-resuscitation injury after cardiac arrest. Laboratory investigations have suggested that induction of hypothermia before return of spontaneous circulation (ROSC) may confer the greatest benefit. We hypothesized that a short delay in resuscitation to induce hypothermia before ROSC, even at the expense of more prolonged ischemia, may yield both physiological and survival advantages. METHODS: Cardiac arrest was induced in C57BL/6 mice using intravenous potassium chloride; resuscitation was attempted with CPR and fluid administration. Animals were randomized into three groups (n=15 each): a normothermic control group, in which 8 min of arrest at 37 degrees C was followed by resuscitation; an early intra-arrest hypothermia group, in which 6.5 min of 37 degrees C arrest were followed by 90s of cooling, with resuscitation attempted at 30 degrees C (8 min total ischemia); and a delayed intra-arrest hypothermia group, with 90s cooling begun after 8 min of 37 degrees C ischemia, so that animals underwent resuscitation at 9.5 min. RESULTS: Animals treated with TH demonstrated improved hemodynamic variables and survival compared to normothermic controls. This was the case even when comparing the delayed intra-arrest hypothermia group with prolonged ischemia time against normothermic controls with shorter ischemia time (7-day survival, 4/15 vs. 0/15, p<0.001). CONCLUSIONS: Short resuscitation delays to allow establishment of hypothermia before ROSC appear beneficial to both cardiac function and survival. This finding supports the concept that post-resuscitation injury processes begin immediately after ROSC, and that intra-arrest cooling may serve as a useful therapeutic approach to improve survival.     

D-dimer assay predicts mortality in critically ill patients without disseminated intravascular coagulation or venous thromboembolic disease

Objective: To determine if D-dimer predicts outcomes in critically ill patients. Design: Observational, cohort study. Setting: Medical intensive care unit (MICU) of a tertiary care hospital. Patients and participants: Seventy-four patients consecutively admitted to the MICU. Interventions: D-dimer was measured by latex agglutination within 12 h of admission to the MICU. Measurements and results: Of the study population, 43.2 % had positive D-dimers. The in-hospital mortality rate in D-dimer positive patients was 28.1 % as compared to 7.1 % in D-dimer negative subjects (p = 0.024). D-dimer positive patients had significantly greater frequencies of venous thromboses (21.9 % vs 4.8 %, p = 0.035). Conclusions: The D-dimer assay identifies patients at increased risk for mortality and may be a more sensitive test to determine the presence of underlying microvascular pathology in critically ill patients. A positive D-dimer at admission to the MICU is associated with an increased risk for the later development of a venous thromboembolic event (VTE). Received: 25 May 1998 Final revision received: 7 October 1998 Accepted: 9 December 1998