Julia Kofler

Outcome and prognostic factors in critically ill cancer patients admitted to the intensive care unit

Objective: To assess survival in cancer patients admitted to an intensive care unit (ICU) with respect to the nature of malignancy, cause of ICU admittance, and course during ICU stay as well as to evaluate the prognostic value of the Acute Physiology and Chronic Health Evaluation (APACHE) III score. Design: Retrospective cohort study. Setting: ICU at a university cancer referral center. Patients: A total of 414 cancer patients admitted to the ICU during a period of 66 months. Interventions: None. Measurements: Charts of the patients were analyzed with respect to underlying disease, cause of admission, APACHE III score, need and duration of mechanical ventilation, neutropenia and development of septic shock, as well as ICU survival and survival after discharge. Mortality data were compared with two control groups: 1362 patients admitted to our ICU suffering from diseases other than cancer and 2,776 cancer patients not admitted to the ICU. Main Results: ICU survival was 53%, and 1‐yr survival was 23%. The 1‐yr mortality rate was significantly lower in both control groups. Patients admitted after bone marrow transplantation had the highest mortality. In a multivariate analysis, prognosis was negatively influenced by respiratory insufficiency, the need of mechanical ventilation, and development of septic shock during the ICU stay. Admission after cardiopulmonary resuscitation yielded high ICU mortality but a relatively good long‐term prognosis. Admission after surgery and as a result of acute hemorrhage was associated with a good prognosis. Age, neutropenia, and underlying disease did not influence outcome significantly. Admission APACHE III scores were significantly higher in nonsurvivors but failed to predict individual outcome satisfactorily. All patients with APACHE III scores of >80 died at the ICU. Conclusion: A combination of factors must be taken into account to estimate a critically ill cancer patients prognosis in the ICU. The APACHE III scoring system alone should not be used to make decisions about therapy prolongation. Admission to the ICU worsens the prognosis of a cancer patient substantially; however, as ICU mortality is 47%, comparable with severely ill noncancer patients, general reluctance to admit cancer patients to an ICU does not seem to be justified.

Accuracy of oscillometric blood pressure measurement according to the relation between cuff size and upper-arm circumference in critically ill patients.

Objective: To evaluate the accuracy of oscillometric blood pressure measurement according to the relation between cuff size and upper‐arm circumference in critically ill patients. Design: Prospective data collection. Setting: Emergency department in a 2,000‐bed inner city hospital. Patients: Thirty‐eight patients categorized into three groups according to their upper‐arm circumference (group I: 18‐25 cm; group II: 25.1‐33 cm; and group III: 33.1‐47.5 cm) were enrolled in the study protocol. Interventions: In each patient, all three cuff sizes (Hewlett‐Packard Cuff 40401 B, C, and D) were used to perform an oscillometric blood pressure measurement at least within 3 mins until ten to 20 measurements for each cuff size were achieved. Invasive mean arterial blood pressure measurement was done by cannulation of the contralateral radial artery with direct transduction of the systemic arterial pressure waveform. The corresponding invasive blood pressure value was obtained at the end of each oscillometric measurement. Measurement and Main Results: Overall, 1,494 pairs of simultaneous oscillometric and invasive blood pressure measurements were collected in 38 patients (group I, n = 5; group II, n = 23; and group III, n = 10) over a total time of 72.3 hrs. Mean arterial blood pressure ranged from 35 to 165 mm Hg. The overall discrepancy between oscillometric and invasive blood pressure measurement was −6.7 ± 9.7 mm Hg (p < .0001), if the recommended cuff size according to the upper‐arm circumference was used (539 measurements). Of all the blood pressure measurements, 26.4% (n = 395) had a discrepancy of ≥10 mm Hg and 34.2% (n = 512) exhibited a discrepancy of ≥20 mm Hg. No differences between invasive and noninvasive blood pressure measurements were noted in patients either with or without inotropic support (−6.6 + 7.2 vs. −8.6 + 6.8 mm Hg; not significant). Conclusion: The oscillometric blood pressure measurement significantly underestimates arterial blood pressure and exhibits a high number of measurements out of the clinically acceptable range. The relation between cuff size and upper‐arm circumference contributes substantially to the inaccuracy of the oscillometric blood pressure measurement. Therefore, oscillometric blood pressure measurement does not achieve adequate accuracy in critically ill patients.

Comparison of prone positioning and continuous rotation of patients with adult respiratory distress syndrome: results of a pilot study.

ObjectiveTo compare prone positioning and continuous rotational therapy with respect to oxygenation and hemodynamics in patients suffering from adult respiratory distress syndrome (ARDS). DesignRandomized, prospective pilot study. SettingIntensive care unit at a university hospital. PatientsTwenty-six mechanically ventilated patients with ARDS from nontraumatic causes. InterventionsTwelve patients were turned prone (group 1), 14 patients underwent continuous axial rotation from one lateral position to the other with a maximum angle of 124 degrees in specially designed beds (group 2). All patients had received inhaled nitric oxide (NO) therapy before positioning. Measurements and Main Results Gas exchange and hemodynamics were assessed using a pulmonary artery catheter. In both groups, an improvement in Pao2/Fio2-ratio and intrapulmonary shunt fraction occurred after initiation of NO as well as during the first 72 hrs of positioning therapy. During the study period, seven patients died in group 1 and nine patients in group 2 (p = NS). Comparing the areas under the curve during the first 72 hrs, no significant differences with respect to Pao2/Fio2-ratio, Paco2, positive end-expiratory and peak inspiratory pressure levels, intrapulmonary shunt fraction, the alveolar-arterial oxygen difference, and oxygen delivery and consumption, as well as cardiac index, pulmonary and arterial blood pressures, and pulmonary arterial occlusion pressure could be detected between the groups. Prone positioning was tolerated well, continuous rotational therapy had to be modified according to hemodynamic instability in three patients. ConclusionsIn severe lung injury, continuous rotational therapy seems to exert effects comparable to prone positioning and could serve as alternative when prone positioning seems inadvisable.

Apolipoprotein E Polymorphism: Survival and Neurological Outcome After Cardiopulmonary Resuscitation

Background and Purpose The apolipoprotein E 3/3 (apoE 3/3) genotype is associated with a reduced risk of developing Alzheimer’s disease and with a favorable neurological outcome after traumatic head injury. In vitro studies suggest that the most common genotype, apoE 3/3, may be involved in neuroprotective and neuroregenerative mechanisms. The aim of this study was to determine whether the apoE 3/3 genotype has an impact on survival and neurological outcome after cardiopulmonary resuscitation. Methods Eighty patients with cardiac arrest were investigated prospectively for their apoE genotype. Epidemiological data were assessed according to recommended guidelines. Patients were divided into 2 groups, ie, with the apoE 3/3 genotype present or absent, and tested for differences in survival and neurological outcome. Further statistical analysis with respect to survival and neurological outcome was performed by using a stepwise logistic regression analysis. Results Patients with the apoE 3/3 genotype had a significantly higher survival rate (64% versus 33%, P =0.007) and more often a favorable neurological outcome (55% versus 27%, P =0.013) compared with patients with other apoE genotypes. The apoE 3/3 genotype was shown to be a substantial predictive factor for a favorable neurological outcome (odds ratio 3.2) and was, apart from other essential factors, predictive for survival (odds ratio 4.4) after cardiopulmonary resuscitation. Conclusions These data give evidence that patients with the apoE 3/3 genotype have a better chance of recovery after cardiopulmonary resuscitation than do patients with apoE genotypes other than 3/3.

Differential effect of PARP-2 deletion on brain injury after focal and global cerebral ischemia

Poly(ADP-ribose) polymerase-2 (PARP-2) is a member of the PARP enzyme family, and, similarly to PARP-1, catalyzes the formation of ADP-ribose polymers in response to DNA damage. While PARP-1 overactivation contributes to ischemic cell death, no information is available regarding the role of PARP-2. In this study, we evaluated the impact of PARP-2 deletion on histopathological outcome from two different experimental models of cerebral ischemia. Male PARP-2−/- mice and wild-type (WT) littermates were subjected to either 2 h of middle cerebral artery occlusion (MCAO) followed by 22 h reperfusion, or underwent 10 mins of KCl-induced cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) and 3-day survival. After MCAO, infarct volume was reduced in PARP-2−/-mice (38% ± 12% of contralateral hemisphere) compared with WT (64% ± 16%). After CA/CPR, PARP-2 deletion significantly increased neuronal cell loss in the hippocampal CA1 field (65% ± 36% ischemic neurons) when compared with WT mice (31% ± 33%), with no effect in either striatum or cortex. We conclude that PARP-2 is a novel executioner of cell death pathways in focal cerebral ischemia, but might be a necessary survival factor after global ischemia to mitigate hippocampal delayed cell death.

Effects of bystander first aid, defibrillation and advanced life support on neurologic outcome and hospital costs in patients after ventricular fibrillation cardiac arrest

Abstract. Objective: To evaluate the effects of basic life support, time to first defibrillation and emergency medical service arrival time on neurologic outcome and expenses for hospital care in patients after cardiac arrest. Setting: Large urban emergency medical services system and emergency department in a 2000-bed university hospital. Design: Outcome and cost benefit analysis of patients admitted to the hospital after witnessed, out-of-hospital, ventricular fibrillation cardiac arrest from October 1, 1991, until December 31, 1997. Patients: Out of 1054 patients with out-of-hospital cardiac arrest, 276 were eligible. Measurements and results: The effects of basic and advanced life support measures on neurologic outcome and hospital expenses were evaluated. In contrast to intubation (odds ratio 1.08; 95% CI: 0.51–2.31; p=0.84), basic life support (odds ratio 0.44; 95% CI: 0.24–0.77; p=0.004) and time to first defibrillation (odds ratio 1.08; 95% CI: 1.03–1.13; p=0.001) were significantly correlated with good neurologic outcome. Among the patients who did not receive basic life support, the average cost per patient with good neurologic outcome significantly increased with the delay of the first defibrillation (p<0.001). Conclusions: In contrast to intubation, bystander basic life support and time to first defibrillation were significantly associated with good neurologic outcome and resulted in fewer expenses spent on in-hospital efforts.

Cardiac arrest with cardiopulmonary resuscitation reduces dendritic spine density in CA1 pyramidal cells and selectively alters acquisition of spatial memory

The hippocampus is highly sensitive to ischemia and is one of the most extensively damaged regions of brain during cardiac arrest. Damage to hippocampus can subsequently lead to learning and memory deficits. The current study used the Morris water maze to characterize spatial learning and memory deficits elicited by 8 min of cardiac arrest with cardiopulmonary resuscitation (CA/CPR) in mice, which is associated with a 25–50% decrease in CA1 neurons. Mice were trained to navigate the water maze prior to CA/CPR or sham surgery (SHAM). They were retested in the water maze on days 7 and 8 postsurgery; both CA/CPR and SHAM groups were able to perform the task at presurgical levels. However, when the hidden platform was moved to a new location, the SHAM mice were able to adapt more quickly to the change and swam a shorter distance in search of the platform than did CA/CPR mice. Thus, CA/CPR did not affect the ability of mice to retain a previously learned platform location, but it did affect their ability to learn a new platform location. This behavioural impairment was correlated with dendritic spine density in the CA1 region of the hippocampus. Data presented here suggest that morphological changes, such as spine density, that occur in neurons that survive CA/CPR may be associated with cognitive impairments.

Dose-dependent neuroprotection by 17β-estradiol after cardiac arrest and cardiopulmonary resuscitation

Objective:Despite recent advances in the treatment of cardiac arrest, neurologic outcome remains poor. 17β-Estradiol (E2) has been widely shown to reduce damage after experimental brain injury. The present study determined whether E2 also improves neuronal survival after experimental cardiac arrest and cardiopulmonary resuscitation and if any protection is dose-dependent. Design:A randomized trial. Setting:A research laboratory. Subjects:Male C57Bl/6 mice weighing 20–25 g. Interventions:Mice were randomized into one of six groups, receiving treatment with 0.5, 2.5, 12.5, 25, or 50 &mgr;g of E2 or vehicle 1.5 mins after return of spontaneous circulation. Ten minutes after induction of cardiac arrest (by KCl injection), cardiopulmonary resuscitation was initiated (with chest compressions, intravenous epinephrine, and ventilation with 100% O2). Additional animals of each E2-treated group were used for plasma estradiol-level analysis. Brains were removed for quantification of injury in the hippocampus and caudoputamen on day 3. Measurements and Main Results:The E2 0.5 group had physiologic estrogen levels 60 min after injection (mean ± se, 28 ± 5 pg/mL), whereas the E2 50 group still showed supraphysiologic levels 360 min after administration (245 ± 32 pg/mL). Hippocampal damage was not altered with E2 treatment. Only posttreatment with the lowest E2 dose (E2 0.5) resulted in attenuated neuronal injury in the rostral and caudal caudoputamen (34 ± 11% and 27 ± 11%), in comparison with vehicle (68 ± 5, p < .05; 63 ± 4%, p < .001). Higher E2 doses did not affect brain injury. Conclusions:We conclude that E2 has a critical dosing effect on neuronal survival, physiologic levels of E2 are neuroprotective after cardiac arrest/cardiopulmonary resuscitation, and acute exposure is sufficient for brain resuscitation.

Simultaneous comparison of thoracic bioimpedance and arterial pulse waveform-derived cardiac output with thermodilution measurement.

Objective To compare the accuracy and reliability of thoracic electrical bioimpedance (TEB) and the arterial pulse waveform analysis with simultaneous measurement of thermodilution cardiac output (TD-CO) in critically ill patients. Design Prospective data collection. Setting Emergency department and critical care unit in a 2,000-bed inner-city hospital. Patients A total of 29 critically ill patients requiring invasive hemodynamic monitoring for clinical management were prospectively studied. Interventions Noninvasive cardiac output was simultaneously measured by a TEB device and by analysis of the arterial pulse waveform derived from the finger artery. Invasive cardiac output was determined by the thermodilution technique. Measurements and Main Results A total of 175 corresponding TD-CO and noninvasive hemodynamic measurements were collected in 30-min intervals. They revealed an overall bias of 0.34 L/min/m2 (95% confidence interval, 0.24–0.44 L/min/m2;p < .001) for the arterial pulse waveform analysis and of 0.61 L/min/m2 (95% confidence interval, 0.50–0.72 L/min/m2;p < .001) for the TEB. In 39.4% (n = 69) of all measurements, the discrepancy between arterial pulse waveform analysis and TD-CO was >0.50 L/min/m2. The discrepancies of the arterial pulse waveform analysis correlated positively with the magnitude of the cardiac index (r2 = 0.29;p < .001). In 56.6% (n = 99) of all measurements, the discrepancy between TEB and TD-CO was >0.50 L/min/m2. The magnitude of the discrepancies of the TEB was significantly correlated with age (r2 = 0.17;p = .02). Measurements were in phase in 93.2% of all arterial pulse waveform analysis and in 84.9% of all TEB readings (p < .001). Conclusions The arterial pulse waveform analysis exhibits a greater accuracy and reliability as compared with the TEB with regard to overall bias, number of inaccurate readings, and phase lags. The arterial pulse waveform analysis may be useful for the monitoring of hemodynamic changes. However, both methods fail to be a substitute for the TD-CO because of a substantial percentage of inaccurate readings.

Cardiopulmonary resuscitation performed by bystanders does not increase adverse effects as assessed by chest radiography.

Important adverse effects of bystander cardiopulmonary resuscitation (CPR) are well known. We describe the number of nonmedical professional CPR-related complications in patients surviving cardiac arrest, as assessed by chest radiograph. Within 2 yr, all consecutive patients admitted to the department of emergency medicine at a university hospital who had a witnessed, nontraumatic, normothermic cardiac arrest were studied. Radiologically evaluated adverse effects were compared with Mann-Whitney U-tests between patients who received bystander basic life support (Bystander group) and patients who did not receive bystander basic life support before advanced life support was started (ALS group). For assessment of bystander CPR-associated complications, chest radiographs were used. Of 224 patients, 173 were eligible. The median age was 58 yr (interquartile range, 51–71 yr), and 126 patients (73%) were men. The incidence of adverse effects associated with assisted-ventilation maneuvers and external chest compressions did not differ significantly between groups (severe gastric insufflation, 17% vs 18% between the Bystander group [n = 59] and the ALS group [n = 96], respectively; suspicion of aspiration, 22% vs 17%, respectively; soft tissue emphysema, 2% vs 1%, respectively; and serial rib fractures, 8% vs 8%, respectively). CPR administered by nonmedical personnel did not increase the number of life support-related adverse effects in patients surviving cardiac arrest as assessed by means of chest radiograph on admission.