Clinical trial of a novel surface cooling system for fever control in neurocritical care patients

OBJECTIVE: To compare the efficacy of a novel water-circulating surface cooling system with conventional measures for treating fever in neuro-intensive care unit patients. DESIGN: Prospective, unblinded, randomized controlled trial. SETTING: Neurologic intensive care unit in an urban teaching hospital. PATIENTS: Forty-seven patients, the majority of whom were mechanically ventilated and sedated, with fever > or =38.3 degrees C for >2 consecutive hours after receiving 650 mg of acetaminophen. INTERVENTIONS: Subjects were randomly assigned to 24 hrs of treatment with a conventional water-circulating cooling blanket placed over the patient (Cincinnati SubZero, Cincinnati OH) or the Arctic Sun Temperature Management System (Medivance, Louisville CO), which employs hydrogel-coated water-circulating energy transfer pads applied directly to the trunk and thighs. MEASUREMENTS AND MAIN RESULTS: Diagnoses included subarachnoid hemorrhage (60%), cerebral infarction (23%), intracerebral hemorrhage (11%), and traumatic brain injury (4%). The groups were matched in terms of baseline variables, although mean temperature was slightly higher at baseline in the Arctic Sun group (38.8 vs. 38.3 degrees C, p = .046). Compared with patients treated with the SubZero blanket (n = 24), Arctic Sun-treated patients (n = 23) experienced a 75% reduction in fever burden (median 4.1 vs. 16.1 C degrees -hrs, p = .001). Arctic Sun-treated patients also spent less percent time febrile (T > or =38.3 degrees C, 8% vs. 42%, p < .001), spent more percent time normothermic (T < or =37.2 degrees C, 59% vs. 3%, p < .001), and attained normothermia faster than the SubZero group median (2.4 vs. 8.9 hrs, p = .008). Shivering occurred more frequently in the Arctic Sun group (39% vs. 8%, p = .013). CONCLUSION: The Arctic Sun Temperature Management System is superior to conventional cooling-blanket therapy for controlling fever in critically ill neurologic patients.     

Higher hemoglobin is associated with improved outcome after subarachnoid hemorrhage

OBJECTIVE: There are few data regarding anemia and transfusion after subarachnoid hemorrhage (SAH). We addressed the hypothesis that higher hemoglobin (HGB) levels are associated with less death and disability after SAH. DESIGN: Prospective registry with automated data retrieval. PATIENTS: Six hundred eleven patients enrolled in the Columbia University SAH Outcomes Project between August 1996 and June 2002. SETTING: Neurologic intensive care unit. INTERVENTIONS: Patients were treated according to standard management protocols. MEASUREMENTS AND MAIN RESULTS: We electronically retrieved all HGB readings during the acute hospital stay for 611 consecutively admitted SAH patients. Outcomes were measured with the modified Rankin Scale at 14 days or discharge, and at 3 months. Patients who were independent (modified Rankin Scale, 0-3) at discharge or 14 days had higher mean (11.7 +/- 1.5 vs. 10.9 +/- 1.2, p < .001) and nadir (9.9 +/- 2.1 vs. 8.6 +/- 1.8, p < .001) HGB, and had higher HGB values every day in the hospital. There were similar results when patients were stratified by mortality. Higher HGB was associated with reduced risk of poor outcome (modified Rankin Scale, 4-6) at 14 days/discharge and 3 months after correcting for Hunt and Hess grade, age, history of diabetes, and cerebral infarction. Length of stay and HGB interacted such that lower HGB has a more pronounced effect with length of stay > 14 days. CONCLUSIONS: Higher HGB values are associated with improved outcomes after SAH at 14 days/discharge and 3 months. In contrast to general critical care patients, SAH patients may benefit from higher HGB. Determination of the optimal goal HGB after SAH will require separate prospective research.     

The Cognitive decline in Older Patients with End stage renal disease (COPE) study – rationale and design

Background: Older patients with end stage renal disease (ESRD) are at increased risk for cognitive decline, but detailed studies of the magnitude of cognitive decline on dialysis or comprehensive conservative management (CCM) are lacking and the underlying pathophysiological mechanisms have poorly been studied.

Objectives: To describe the rationale and design of the COPE study. Study objectives are as follows. Firstly, to examine the severity of cognitive impairment in older patients reaching ESRD before dialysis and the rate of decline after dialysis or CCM initiation. Secondly, to study the association of blood biomarkers for microvascular damage and MRI derived measurements of small vessel disease with the rate of cognitive decline. Thirdly, to examine to what extent cardiac function is related to brain structure and perfusion in patients reaching ESRD. Finally, to study the association of cognitive and functional capacity with quality of life in pre-dialysis patients, as well as after dialysis or CCM initiation.

Study design and methods: The COPE study is a prospective, multicenter cohort study in the Netherlands, including prevalent and incident pre-dialysis patients ≥65 years old with eGFR ≤20?ml/min/1.73 m², awaiting either dialysis or CCM initiation. At baseline extensive data is collected including a comprehensive geriatric assessment and laboratory tests. Brain and cardiac MRI for analysis of structural and functional abnormalities are performed at baseline and repeated following therapy change. All other measurements are repeated annually during four years of follow up, including an extra evaluation six months after initiation of dialysis.

Conclusions: Knowledge of the magnitude of cognitive decline and its underlying pathophysiological mechanism, as well as its impact on functionality and quality of life can eventually help to postulate an algorithm for well balanced decision making in treatment strategies in older patients reaching ESRD.

Clinical trial registration: The COPE study is registered on www.ccmo.nl (number: NL46389.058.13).     

A multicenter,prospective, randomized,double‐blind,placebo‐controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma

Objective

The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence‐based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc.

Methods

Forty‐five patients were randomized to receive low‐dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single‐breath diffusing capacity for carbon monoxide (DLCO ). Secondary outcome measures included changes in appearance on high‐resolution computed tomography and dyspnea scores. An intent‐to‐treat statistical analysis was performed.

Results

At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty‐two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non–trial‐related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between‐group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLCO or secondary outcome measures were identified.

Conclusion

This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low‐dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events.

     

In nonhuman primates intracarotid adenosine, but not sodium nitroprusside, increases cerebral blood flow.

Intracarotid infusion of short-acting vasodilators, such as adenosine and nitroprusside, in doses that lack significant systemic side effects, may permit controlled manipulation of cerebrovascular resistance. In this experiment we assessed changes in cerebral blood flow (CBF) after intracarotid infusion of nitroprusside and adenosine. The study was conducted on six adult baboons under isoflurane anesthesia and controlled ventilation. Intracarotid drug infusion protocol avoided hypotension during nitroprusside infusion and tested for autoregulatory vasoconstriction. CBF (intraarterial (133)Xe technique) was measured four times during infusions of 1) intracarotid saline, 2) IV phenylephrine (0.2 microg x kg(-1) x min(-1)) aimed to increase mean arterial pressure by 10-15 mm Hg, 3) IV phenylephrine and intracarotid nitroprusside (0.5 microg x kg(-1) x min(-1)), and 4) intracarotid adenosine (1 mg/min). IV phenylephrine increased mean arterial pressure (69 +/- 8 to 91 +/- 9 mm Hg, P < 0.0001, n = 6), and concurrent infusion of intracarotid nitroprusside reversed this effect. However, compared with baseline, CBF did not change with IV phenylephrine or with concurrent infusion of IV phenylephrine and intracarotid nitroprusside. Intracarotid adenosine profoundly increased CBF (from 29 +/- 8 to 75 +/- 32 mL x 100 g(-1) x min(-1); P < 0.0001). In nonhuman primates, intracarotid adenosine increases CBF in doses that lack significant systemic side effects, whereas intracarotid nitroprusside has no effect. Intracarotid adenosine may be useful for manipulating cerebrovascular resistance and augmenting CBF during cerebral ischemia. IMPLICATIONS: Intraarterial (133)Xe cerebral blood flow (CBF) measurements suggest that intracarotid adenosine, in a dose that lacks significant systemic side effects, profoundly increases CBF, whereas nitroprusside has no effect.(5-12)     

Impact of medical complications on outcome after subarachnoid hemorrhage

OBJECTIVE: Medical complications occur frequently after subarachnoid hemorrhage (SAH). Their impact on outcome remains poorly defined. DESIGN: Inception cohort study. PATIENTS: Five-hundred eighty patients enrolled in the Columbia University SAH Outcomes Project between July 1996 and May 2002. SETTING: Neurologic intensive care unit. INTERVENTIONS: Patients were treated according to standard management protocols. MEASUREMENTS AND MAIN RESULTS: Poor outcome was defined as death or severe disability (modified Rankin score, 4-6) at 3 months. We calculated the frequency of medical complications according to prespecified criteria and evaluated their impact on outcome, using forward stepwise multiple logistic regression after adjusting for known predictors of poor outcome. Thirty-eight% had a poor outcome; mortality was 21%. The most frequent complications were temperature>38.3 degreesC (54%), followed by anemia treated with transfusion (36%), hyperglycemia>11.1 mmol/L (30%), treated hypertension (>160 mm Hg systolic; 27%), hypernatremia>150 mmol/L (22%), pneumonia (20%), hypotension (<90 mm Hg systolic) treated with vasopressors (18%), pulmonary edema (14%), and hyponatremia<130 mmol/L (14%). Fever (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.4; p=.02), anemia (OR, 1.8; 95% CI, 1.1-2.9; p=.02), and hyperglycemia (OR, 1.8; 95% CI, 1.1-3.0; p=.02) significantly predicted poor outcome after adjustment for age, Hunt-Hess grade, aneurysm size, rebleeding, and cerebral infarction due to vasospasm. CONCLUSIONS: Fever, anemia, and hyperglycemia affect 30% to 54% of patients with SAH and are significantly associated with mortality and poor functional outcome. Critical care strategies directed at maintaining normothermia, normoglycemia, and prevention of anemia may improve outcome after SAH.     

Nursing education changes and reduced standards of quality care

In acknowledging the evidence pointing to decreased standards of care, the authors accept the need to address identified problems. However, quality resolution will not occur by solely overhauling nurse education. The sum and substance of nursing requires that all key players influencing pre-registration nurse education must own their part in the problem. This paper addresses the main players, aims to define their roles and identifies the strategies necessary to address these serious concerns. National debate is required as is specific role identification. However, this will be to no avail if leadership, monitoring and the application of sanctions for non-compliance are not reinstated at both national and local levels.