Causes of death and determinants of outcome in critically ill patients

INTRODUCTION: Whereas most studies focus on laboratory and clinical research, little is known about the causes of death and risk factors for death in critically ill patients. METHODS: Three thousand seven hundred patients admitted to an adult intensive care unit (ICU) were prospectively evaluated. Study endpoints were to evaluate causes of death and risk factors for death in the ICU, in the hospital after discharge from ICU, and within one year after ICU admission. Causes of death in the ICU were defined according to standard ICU practice, whereas deaths in the hospital and at one year were defined and grouped according to the ICD-10 (International Statistical Classification of Diseases and Related Health Problems) score. Stepwise logistic regression analyses were separately calculated to identify independent risk factors for death during the given time periods. RESULTS: Acute, refractory multiple organ dysfunction syndrome was the most frequent cause of death in the ICU (47%), and central nervous system failure (relative risk [RR] 16.07, 95% confidence interval [CI] 8.3 to 31.4, p < 0.001) and cardiovascular failure (RR 11.83, 95% CI 5.2 to 27.1, p < 0.001) were the two most important risk factors for death in the ICU. Malignant tumour disease and exacerbation of chronic cardiovascular disease were the most frequent causes of death in the hospital (31.3% and 19.4%, respectively) and at one year (33.2% and 16.1%, respectively). CONCLUSION: In this primarily surgical critically ill patient population, acute or chronic multiple organ dysfunction syndrome prevailed over single-organ failure or unexpected cardiac arrest as a cause of death in the ICU. Malignant tumour disease and chronic cardiovascular disease were the most important causes of death after ICU discharge.

Is alcohol ablation of the septum associated with recurrent tachyarrhythmias?

QUESTIONS UNDER STUDY: Alcohol ablation (AA) of the septum has been introduced as new therapy in hypertrophic cardiomyopathy (HCM). It was feared that iatrogenic myocardial infarction due to AA may induce re-entry tachyarrhythmias and increase sudden cardiac death. METHODS AND RESULTS: Twenty-four patients (mean age 52 years) underwent successful AA. Clinical follow-up (FU) ranged from 0.3 to 0.7 years (mean 2.8). One patient died (suicide) 4 years after AA. Left ventricular (LV) outflow gradient (peak-to-peak) decreased (median) after AA from 43 (IQR 25 to 4) mmHg to 1 (IQR 0 to 12) mmHg (rest) (p <0.001) and from 130 (IQR 75 to 165) mmHg to 13 (IQR 0 to 31) mmHg (postextrasystolic) (p <0.001). Transient AV block occurred in 22% (5/24) necessitating temporary pacing. A permanent pacemaker was implanted in 4% (1/24). NYHA-class was 2.5 (IQR 2.0 to 3.0) before and 1.5 (IQR 1.3 to 2.0) (p <0.001) after AA. During FU, 2 pacemakers were implanted due to bradycardia (no AV block). A right bundle branch block was found in 13% (2/24) before and 46 % (11/24) after AA (p = 0.003). Non-sustained ventricular tachycardia (NSVT) was observed in 13% (2/16) before and 22% (5/23) (p = 0.46) after AA. Two patients required ICD implantation. CONCLUSIONS: Long-term FU is excellent in HCM after AA. The pressure gradient drops below 25 mm Hg in 95% (23/24) of all patients. Transient AV block occurs in 22% (5/24), but permanent pacemaker implantation is rarely needed (13%, 2/24). Severe NSVT occurs in 13% (2/16) before and 22% (5/23) after AA but ICD implantation is only occasionally required.

Methylprednisolone Fails to Preserve Pulmonary Surfactant and Blood-Air Barrier Integrity in a Porcine Cardiopulmonary Bypass Model

BACKGROUND: Pulmonary inflammation after cardiac surgery with cardiopulmonary bypass (CPB) has been linked to respiratory dysfunction and ultrastructural injury. Whether pretreatment with methylprednisolone (MP) can preserve pulmonary surfactant and blood-air barrier, thereby improving pulmonary function, was tested in a porcine CPB-model. MATERIALS AND METHODS: After randomizing pigs to placebo (PLA; n = 5) or MP (30 mg/kg, MP; n = 5), animals were subjected to 3 h of CPB with 1 h of cardioplegic cardiac arrest. Hemodynamic data, plasma tumor necrosis factor-alpha (TNF-alpha, ELISA), and pulmonary function parameters were assessed before, 15 min after CPB, and 8 h after CPB. Lung biopsies were analyzed for TNF-alpha (Western blot) or blood-air barrier and surfactant morphology (electron microscopy, stereology). RESULTS: Systemic TNF-alpha increased and cardiac index decreased at 8 h after CPB in PLA (P < 0.05 versus pre-CPB), but not in MP (P < 0.05 versus PLA). In both groups, at 8 h after CPB, PaO(2) and PaO(2)/FiO(2) were decreased and arterio-alveolar oxygen difference and pulmonary vascular resistance were increased (P < 0.05 versus baseline). Postoperative pulmonary TNF-alpha remained unchanged in both groups, but tended to be higher in PLA (P = 0.06 versus MP). The volume fraction of inactivated intra-alveolar surfactant was increased in PLA (58 +/- 17% versus 83 +/- 6%) and MP (55 +/- 18% versus 80 +/- 17%) after CPB (P < 0.05 versus baseline for both groups). Profound blood-air barrier injury was present in both groups at 8 h as indicated by an increased blood-air barrier integrity score (PLA: 1.28 +/- 0.03 versus 1.70 +/- 0.1; MP: 1.27 +/- 0.08 versus 1.81 +/- 0.1; P < 0.05). CONCLUSION: Despite reduction of the systemic inflammatory response and pulmonary TNF-alpha generation, methylprednisolone fails to decrease pulmonary TNF-alpha and to preserve pulmonary surfactant morphology, blood-air barrier integrity, and pulmonary function after CPB.

Meperidine and skin surface warming additively reduce the shivering threshold: a volunteer study

INTRODUCTION: Mild therapeutic hypothermia has been shown to improve outcome for patients after cardiac arrest and may be beneficial for ischaemic stroke and myocardial ischaemia patients. However, in the awake patient, even a small decrease of core temperature provokes vigorous autonomic reactions-vasoconstriction and shivering-which both inhibit efficient core cooling. Meperidine and skin warming each linearly lower vasoconstriction and shivering thresholds. We tested whether a combination of skin warming and a medium dose of meperidine additively would reduce the shivering threshold to below 34 degrees C without producing significant sedation or respiratory depression. METHODS: Eight healthy volunteers participated on four study days: (1) control, (2) skin warming (with forced air and warming mattress), (3) meperidine (target plasma level: 0.9 mug/ml), and (4) skin warming plus meperidine (target plasma level: 0.9 mug/ml). Volunteers were cooled with 4 degrees C cold Ringer lactate infused over a central venous catheter (rate asymptotically equal to 2.4 degrees C/hour core temperature drop). Shivering threshold was identified by an increase of oxygen consumption (+20% of baseline). Sedation was assessed with the Observer's Assessment of Alertness/Sedation scale. RESULTS: Control shivering threshold was 35.5 degrees C +/- 0.2 degrees C. Skin warming reduced the shivering threshold to 34.9 degrees C +/- 0.5 degrees C (p = 0.01). Meperidine reduced the shivering threshold to 34.2 degrees C +/- 0.3 degrees C (p < 0.01). The combination of meperidine and skin warming reduced the shivering threshold to 33.8 degrees C +/- 0.2 degrees C (p < 0.01). There were no synergistic or antagonistic effects of meperidine and skin warming (p = 0.59). Only very mild sedation occurred on meperidine days. CONCLUSION: A combination of meperidine and skin surface warming reduced the shivering threshold to 33.8 degrees C +/- 0.2 degrees C via an additive interaction and produced only very mild sedation and no respiratory toxicity.

[Manifestation and course of coronary heart disease in men and women--consequences for diagnosis and treatment]

Gender related issues in manifestation, diagnosis and treatment of coronary artery disease are important but still not well recognized. Women are more likely to present late after first symptoms of myocardial infarction. Myocardial infarction is more often unrecognized. In regard to complications after myocardial infarctions ventricular tachycardia and cardiac arrest are more frequent and women are also more likely to develop heart failure or cardiogenic shock. The reason for this is most probably the fact that women presenting with myocardial infarction are of older age and have a higher incidence of co-morbidities. Thrombolysis and coronary angioplasty are less often performed in women in the setting of myocardial infarction. However there is a clear trend toward improvement of this situation during the last years. The reopening rate of occluded coronary arteries with thrombolysis and with coronary angioplasty is similar in women compared to men. Perioperative risk with aorto-coronary bypass surgery is higher in women, which can not be fully explained by higher age and co-morbidities. However 10 years survival rate after aorto-coronary bypass-surgery is similar for men and women, although occlusion of venous grafts is seen more often in women. The benefit of structured cardiac rehabilitation after an acute event is similar for younger and older women and as good as in men. Positive effects of cardiac rehabilitation include increased physical performance, reduction of body fat, improvement of lipid-profiles and an improvement of the psychosocial situation and quality of life.

Effect of chest compressions only during experimental basic life support on alveolar collapse and recruitment

AIM: The importance of ventilatory support during cardiac arrest and basic life support is controversial. This experimental study used dynamic computed tomography (CT) to assess the effects of chest compressions only during cardiopulmonary resuscitation (CCO-CPR) on alveolar recruitment and haemodynamic parameters in porcine model of ventricular fibrillation. MATERIALS AND METHODS: Twelve anaesthetized pigs (26+/-1kg) were randomly assigned to one of the following groups: (1) intermittent positive pressure ventilation (IPPV) both during basic life support and advanced cardiac life support, or (2) CCO during basic life support and IPPV during advanced cardiac life support. Measurements were acquired at baseline prior to cardiac arrest, during basic life support, during advanced life support, and after return of spontaneous circulation (ROSC), as follows: dynamic CT series, arterial and central venous pressures, blood gases, and regional organ blood flow. The ventilated and atelectatic lung area was quantified from dynamic CT images. Differences between groups were analyzed using the Kruskal-Wallis test, and a p<0.05 was considered statistically significant. RESULTS: IPPV was associated with cyclic alveolar recruitment and de-recruitment. Compared with controls, the CCO-CPR group had a significantly larger mean fractional area of atelectasis (p=0.009), and significantly lower PaO(2) (p=0.002) and mean arterial pressure (p=0.023). The increase in mean atelectatic lung area observed during basic life support in the CCO-CPR group remained clinically relevant throughout the subsequent advanced cardiac life support period and following ROSC, and was associated with prolonged impaired haemodynamics. No inter-group differences in myocardial and cerebral blood flow were observed. CONCLUSION: A lack of ventilation during basic life support is associated with excessive atelectasis, arterial hypoxaemia and compromised CPR haemodynamics. Moreover, these detrimental effects remain evident even after restoration of IPPV.

[Is resting heart rate a cardiovascular risk factor?]

During recent years, resting heart rate was not considered as a cardiovascular risk factor. However, new evidences have showed that resting heart rate is an important prognostic factor for sudden cardiac death and heart failure in the general population, and especially among patients with known cardiac disease. Interestingly, resting heart rate not only predicts cardiac mortality but also all-cause mortality. The most common pathophysiological explanation is related to the fact that increased heart rate increases myocardial oxygen consumption and in parallel reduces coronary blood flow (reduction in the diastolic duration).

Serological evidence for the association of Bartonella henselae infection with arrhythmogenic right ventricular cardiomyopathy

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in young adults. On the basis of histopathological findings its pathogenesis may involve both a genetic origin and an inflammatory process. Bartonella henselae may cause endomyocarditis and was detected in myocardium from a young male who succumbed to sudden cardiac death. HYPOTHESIS: We hypothesized that chronic infection with Bartonella henselae could contribute to the pathogenesis of ARVC. METHODS: We investigated sera from 49 patients with ARVC for IgG antibodies to Bartonella henselae. In this study, 58 Swiss blood donors tested by the same method served as controls. RESULTS: Six patients with ARVC (12%) had positive (>1:256) IgG titres in the immunofluorescence test with Bartonella henselae. In contrast, only 1 elevated titre was found in 58 controls (p < or = 0.05). Interestingly, all patients with increased titres had no familial occurrence of ARVC. CONCLUSIONS: Further studies in larger patient cohorts seem justified to investigate a possible causal link between chronic Bartonella henselae and ARVC, in particular its sporadic (nonfamilial) form.

Thermoregulatory management for mild therapeutic hypothermia

In recent years the use of mild therapeutic hypothermia as a means of neuroprotection has become an important concept for treatment after cerebral ischemic hypoxic injury. Mild therapeutic hypothermia has been shown to improve outcome after out-of-hospital cardiac arrest, and many studies suggest a beneficial effect of mild therapeutic hypothermia on patient outcome after traumatic brain injury, cerebrovascular damage and neonatal asphyxia. This review article explores the numerous possibilities and methods for the induction of mild therapeutic hypothermia, reviews thermoregulatory management during maintenance and discusses associated risks and complications.

Addition of dextran sulfate to blood cardioplegia attenuates reperfusion injury in a porcine model of cardiopulmonary bypass

OBJECTIVE: Contact of blood with artificial surfaces and air as well as ischemia/reperfusion injury to the heart and lungs mediate systemic and local inflammation during cardiopulmonary bypass (CPB). Activation of complement and coagulation cascades leads to and accompanies endothelial cell damage. Therefore, endothelial-targeted cytoprotection with the complement inhibitor and endothelial protectant dextran sulfate (DXS, MW 5000) may attenuate CBP-associated myocardial and pulmonary injury. METHODS: Eighteen pigs (DXS, n=10; phosphate buffered saline [PBS], n=8) underwent standard cardiopulmonary bypass. After aortic cross-clamping, cardiac arrest was initiated with modified Buckberg blood cardioplegia (BCP), repeated after 30 and 60 min with BCP containing either DXS (300 mg/10 ml, equivalent to 5mg/kg) or 10 ml of PBS. Following 30 min reperfusion, pigs were weaned from CPB. During 2h of observation, cardiac function was monitored by echocardiography and invasive pressure measurements. Inflammatory and coagulation markers were assessed regularly. Animals were then sacrificed and heart and lungs analyzed. RESULTS: DXS significantly reduced CK-MB levels (43.4+/-14.8 ng/ml PBS, 35.9+/-11.1 ng/ml DXS, p=0.042) and significantly diminished cytokine release: TNFalpha (1507.6+/-269.2 pg/ml PBS, 222.1+/-125.6 pg/ml DXS, p=0.0071), IL1beta (1081.8+/-203.0 pg/ml PBS, 110.7+/-79.4 pg/ml DXS, p=0.0071), IL-6 (173.0+/-91.5 pg/ml PBS, 40.8+/-19.4 pg/ml DXS, p=0.002) and IL-8 (304.6+/-81.3 pg/ml PBS, 25.4+/-14.2 pg/ml DXS, p=0.0071). Tissue endothelin-1 levels were significantly reduced (6.29+/-1.90 pg/100mg PBS, 3.55+/-1.15 pg/100mg DXS p=0.030) as well as thrombin-anti-thrombin formation (20.7+/-1.0 microg/ml PBS, 12.8+/-4.1 microg/ml DXS, p=0.043). Also DXS reduced cardiac and pulmonary complement deposition, neutrophil infiltration, hemorrhage and pulmonary edema (measured as lung water content, 81+/-3% vs 78+/-3%, p=0.047), indicative of attenuated myocardial and pulmonary CPB-injury. Diastolic left ventricular function (measured as dp/dt(min)), pulmonary artery pressure (21+/-3 mmHg PBS, 19+/-3 mmHg DXS, p=0.002) and right ventricular pressure (21+/-1 mmHg PBS, 19+/-3 mmHg DXS p=0.021) were significantly improved with the use of DXS. CONCLUSIONS: Addition of DXS to the BCP solution ameliorates post-CPB injury and to a certain extent improves cardiopulmonary function. Endothelial protection in addition to myocyte protection may improve post-CPB outcome and recovery.

Excellent outcome after surgical treatment of massive pulmonary embolism in critically ill patients

OBJECTIVE: Treatment of central and paracentral pulmonary embolism in patients with hemodynamic compromise remains a subject of debate, and no consensus exists regarding the best method: thrombolytic agents, catheter-based thrombus aspiration or fragmentation, or surgical embolectomy. We reviewed our experience with emergency surgical pulmonary embolectomy. METHODS: Between January of 2000 and March of 2007, 25 patients (17 male, mean age 60 years) underwent emergency open embolectomy for central and paracentral pulmonary embolism. Eighteen patients presented in cardiogenic shock, 8 of whom had cardiac arrest and required cardiopulmonary resuscitation. All patients underwent operation with mild hypothermic cardiopulmonary bypass. Concomitant procedures were performed in 8 patients (3 coronary artery bypass grafts, 2 patent foramen ovale closures, 4 ligations of the left atrial appendage, 3 removals of a right atrial thrombus). Follow-up is 96% complete with a median of 2 years (range, 2 months to 6 years). RESULTS: All patients survived the procedure, but 2 patients died in the hospital on postoperative days 1 (intracerebral bleeding) and 11 (multiorgan failure), accounting for a 30-day mortality of 8% (95% confidence interval: 0.98-0.26). Four patients died later because of their underlying disease. Pre- and postoperative echocardiographic pressure measurements demonstrated the reduction of the pulmonary hypertension to half of the systemic pressure values or less. CONCLUSION: Surgical pulmonary embolectomy is an excellent option for patients with major pulmonary embolism and can be performed with minimal mortality and morbidity. Even patients who present with cardiac arrest and require preoperative cardiopulmonary resuscitation show satisfying results. Immediate surgical desobstruction favorably influences the pulmonary pressure and the recovery of right ventricular function, and remains the treatment of choice for patients with massive central and paracentral embolism with hemodynamic and respiratory compromise.

Termination of Ventricular Tachycardia with Antitachycardia Pacing after Ineffective Shock Therapy in an ICD Recipient with Hypertrophic Cardiomyopathy

Implantable Cardioverter Defibrillator (ICD) implantation is the only established therapy for primary or secondary prevention of sudden cardiac death in patients with Hypertrophic Cardiomyopathy (HCM). Ineffectiveness of shock therapy for the termination of potentially fatal ventricular arrhythmias in ICD recipients is rare in the presence of appropriate arrhythmia detection by the device. We report the case of a 48-year-old woman with HCM and a single chamber ICD, who received five inefficient high-energy (35 Joules) shocks for the termination of an appropriately detected episode of Ventricular Tachycardia (VT). The episode was safely terminated with a subsequent application of Antitachycardia Pacing (ATP) by the device. At the following ICD control, an acceptable defibrillation threshold was detected.

Hands-on time during cardiopulmonary resuscitation is affected by the process of teambuilding: A prospective randomised simulator-based trial

Background Cardiac arrests are handled by teams rather than by individual health-care workers. Recent investigations demonstrate that adherence to CPR guidelines can be less than optimal, that deviations from treatment algorithms are associated with lower survival rates, and that deficits in performance are associated with shortcomings in the process of team-building. The aim of this study was to explore and quantify the effects of ad-hoc team-building on the adherence to the algorithms of CPR among two types of physicians that play an important role as first responders during CPR: general practitioners and hospital physicians. Methods To unmask team-building this prospective randomised study compared the performance of preformed teams, i.e. teams that had undergone their process of team-building prior to the onset of a cardiac arrest, with that of teams that had to form ad-hoc during the cardiac arrest. 50 teams consisting of three general practitioners each and 50 teams consisting of three hospital physicians each, were randomised to two different versions of a simulated witnessed cardiac arrest: the arrest occurred either in the presence of only one physician while the remaining two physicians were summoned to help ("ad-hoc"), or it occurred in the presence of all three physicians ("preformed"). All scenarios were videotaped and performance was analysed post-hoc by two independent observers. Results Compared to preformed teams, ad-hoc forming teams had less hands-on time during the first 180 seconds of the arrest (93 ± 37 vs. 124 ± 33 sec, P < 0.0001), delayed their first defibrillation (67 ± 42 vs. 107 ± 46 sec, P < 0.0001), and made less leadership statements (15 ± 5 vs. 21 ± 6, P < 0.0001). Conclusion Hands-on time and time to defibrillation, two performance markers of CPR with a proven relevance for medical outcome, are negatively affected by shortcomings in the process of ad-hoc team-building and particularly deficits in leadership. Team-building has thus to be regarded as an additional task imposed on teams forming ad-hoc during CPR. All physicians should be aware that early structuring of the own team is a prerequisite for timely and effective execution of CPR.

Multivessel versus culprit vessel percutaneous coronary intervention in ST-elevation myocardial infarction: is more worse?

Aims: We examined what type of STEMI patients are more likely to undergo multivessel PCI (MPCI) in a "real-world" setting and whether MPCI leads to worse or better outcomes compared with single-vessel PCI (SPCI) after stratifying patients by risk. Methods and results: Among STEMI patients enrolled in the Swiss AMIS Plus registry between 2005 and 2012 (n=12,000), 4,941 were identified with multivessel disease. We then stratified patients based on MPCI use and their risk. High-risk patients were identified a priori as those with: 1) left main (LM) involvement (lesions, n=263); 2) out-of-hospital cardiac arrest; or 3) Killip class III/IV. Logistic regression models examined for predictors of MPCI use and the association between MPCI and in-hospital mortality. Three thousand eight hundred and thirty-three (77.6%) patients underwent SPCI and 1,108 (22.4%) underwent MPCI. Rates of MPCI were greater among high-risk patients for each of the three categories: 8.6% vs. 5.9% for out-of-hospital cardiac arrest (p<0.01); 12.3% vs. 6.2% for Killip III/IV (p<0.001); and 14.5% vs. 2.7% for LM involvement (p<0.001). Overall, in-hospital mortality after MPCI was higher when compared with SPCI (7.3% vs. 4.4%; p<0.001). However, this result was not present when patients were stratified by risk: in-hospital mortality for MPCI vs. SPCI was 2.0% vs. 2.0% (p=1.00) in low-risk patients and 22.2% vs. 21.7% (p=1.00) in high-risk patients. Conclusions: High-risk patients are more likely to undergo MPCI. Furthermore, MPCI does not appear to be associated with higher mortality after stratifying patients based on their risk.

Different Prognostic Value of Functional Right Ventricular Parameters in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

BACKGROUND -The value of standard two-dimensional transthoracic echocardiographic (TTE) parameters for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is controversial. METHODS AND RESULTS -We investigated the impact of right ventricular fractional area change (FAC) and tricuspid annulus plane systolic excursion (TAPSE) for prediction of major adverse cardiovascular events (MACE) defined as the occurrence of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia or arrhythmogenic syncope. Among 70 patients who fulfilled the 2010 ARVC/D Task Force Criteria and underwent baseline TTE, 37 (53%) patients experienced a MACE during a median follow-up period of 5.3 (IQR 1.8-9.8) years. Average values for FAC, TAPSE, and TAPSE indexed to body surface area (BSA) decreased over time (p=0.03 for FAC, p=0.03 for TAPSE and p=0.01 for TAPSE/BSA, each vs. baseline). In contrast, median right ventricular end-diastolic area (RVEDA) increased (p=0.001 vs. baseline). Based on the results of Kaplan-Meier estimates, the time between baseline TTE and experiencing MACE was significantly shorter for patients with FAC <23% (p<0.001), TAPSE <17mm (p=0.02) or right atrial (RA) short axis/BSA ≥25mm/m(2) (p=0.04) at baseline. A reduced FAC constituted the strongest predictor of MACE (hazard ratio 1.08 per 1% decrease; 95% confidence interval 1.04-1.12; p<0.001) on bivariable analysis. CONCLUSIONS -This long-term observational study indicates that TAPSE and dilation of right-sided cardiac chambers are associated with an increased risk for MACE in ARVC/D patients with advanced disease and a high risk for adverse events. However, FAC is the strongest echocardiographic predictor of adverse outcome in these patients. Our data advocate a role for TTE in risk stratification in patients with ARVC/D, although our results may not be generalizable to lower risk ARVC/D cohorts.