Rebecca M. Bauer

Perioperative Blood Transfusion and Radical Cystectomy: Does Timing of Transfusion Affect Bladder Cancer Mortality?

BACKGROUND While perioperative blood transfusion (BT) has been associated with adverse outcomes in multiple malignancies, the importance of BT timing has not been established. OBJECTIVE The objective of this study was to evaluate whether intraoperative BT is associated with worse cancer outcomes in bladder cancer patients treated with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS Outcomes from two independent cohorts of consecutive patients with bladder cancer treated with RC were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Recurrence-free survival, cancer-specific survival (CSS), and overall survival were estimated and multivariate analyses were performed to evaluate the association of BT timing with cancer outcomes. RESULTS AND LIMITATIONS In the primary cohort of 360 patients, 241 (67%) received perioperative BT, including 162 intraoperatively and 79 postoperatively. Five-year CSS was 44% among patients who received an intraoperative BT versus 64% for patients who received postoperative BT (p=0.0005). After multivariate analysis, intraoperative BT was associated with an increased risk of cancer mortality (hazard ratio [HR]: 1.93; p=0.02), while receipt of postoperative BT was not (p=0.60). In the validation cohort of 1770 patients, 1100 (62%) received perioperative BT with a median postoperative follow-up of 11 yr (interquartile range: 8.0-15.7). Five-year RFS (p<0.001) and CSS (p<0.001) were significantly worse among patients who received an intraoperative BT. Intraoperative BT was independently associated with recurrence (HR: 1.45; p=0.001), cancer-specific mortality (HR: 1.55; p=0.0001), and all-cause mortality (HR: 1.40; p<0.0001). Postoperative BT was not associated with risk of disease recurrence or cancer death. CONCLUSIONS Intraoperative BT is associated with increased risk of bladder cancer recurrence and mortality. PATIENT SUMMARY In this study, the effects of blood transfusion on bladder cancer surgery outcomes were evaluated. Intraoperative blood transfusion, but not postoperative transfusion, was associated with higher rates of recurrence and cancer-specific mortality.

Surveillance neuroimaging and neurologic examinations affect care for intracerebral hemorrhage

Objective: We tested the hypothesis that surveillance neuroimaging and neurologic examinations identified changes requiring emergent surgical interventions in patients with intracerebral hemorrhage (ICH). Methods: Patients with primary ICH were enrolled into a prospective registry between December 2006 and July 2012. Patients were managed in a neuroscience intensive care unit with a protocol that included serial neuroimaging at 6, 24, and 48 hours, and hourly neurologic examinations using the Glasgow Coma Scale and NIH Stroke Scale. We evaluated all cases of craniotomy and ventriculostomy to determine whether the procedure was part of the initial management plan or occurred subsequently. For those that occurred subsequently, we determined whether worsening on neurologic examination or worsened neuroimaging findings initiated the process leading to intervention. Results: There were 88 surgical interventions in 84 (35%) of the 239 patients studied, including ventriculostomy in 52 (59%), craniotomy in 21 (24%), and both in 11 (13%). Of the 88 interventions, 24 (27%) occurred subsequently and distinctly from initial management, a median of 15.9 hours (8.9–27.0 hours) after symptom onset. Thirteen (54%) were instigated by findings on neurologic examination and 11 (46%) by neuroimaging. Demographics, severity of hemorrhage, and hemorrhage location were not associated with delayed intervention. Conclusions: More than 25% of surgical interventions performed after ICH were prompted by delayed imaging or clinical findings. Serial neurologic examinations and neuroimaging are important and effective surveillance techniques for monitoring patients with ICH.

Incidence of Connected Consciousness after Tracheal Intubation: A Prospective, International, Multicenter Cohort Study of the Isolated Forearm Technique.

Background: The isolated forearm technique allows assessment of consciousness of the external world (connected consciousness) through a verbal command to move the hand (of a tourniquet-isolated arm) during intended general anesthesia. Previous isolated forearm technique data suggest that the incidence of connected consciousness may approach 37% after a noxious stimulus. The authors conducted an international, multicenter, pragmatic study to establish the incidence of isolated forearm technique responsiveness after intubation in routine practice. Methods: Two hundred sixty adult patients were recruited at six sites into a prospective cohort study of the isolated forearm technique after intubation. Demographic, anesthetic, and intubation data, plus postoperative questionnaires, were collected. Univariate statistics, followed by bivariate logistic regression models for age plus variable, were conducted. Results: The incidence of isolated forearm technique responsiveness after intubation was 4.6% (12/260); 5 of 12 responders reported pain through a second hand squeeze. Responders were younger than nonresponders (39 ± 17 vs. 51 ± 16 yr old; P = 0.01) with more frequent signs of sympathetic activation (50% vs. 2.4%; P = 0.03). No participant had explicit recall of intraoperative events when questioned after surgery (n = 253). Across groups, depth of anesthesia monitoring values showed a wide range; however, values were higher for responders before (54 ± 20 vs. 42 ± 14; P = 0.02) and after (52 ± 16 vs. 43 ± 16; P = 0.02) intubation. In patients not receiving total intravenous anesthesia, exposure to volatile anesthetics before intubation reduced the odds of responding (odds ratio, 0.2 [0.1 to 0.8]; P = 0.02) after adjustment for age. Conclusions: Intraoperative connected consciousness occurred frequently, although the rate is up to 10-times lower than anticipated. This should be considered a conservative estimate of intraoperative connected consciousness.

Predictors of 30-day readmission after intracerebral hemorrhage: a single-center approach for identifying potentially modifiable associations with readmission.

Objective:To determine whether patient’s demographics or severity of illness predict hospital readmission within 30 days following spontaneous intracerebral hemorrhage, to identify readmission associations that may be modifiable at the single-center level, and to determine the impact of readmission on outcomes. Design:We collected demographic, clinical, and hospital course data for consecutive patients with spontaneous intracerebral hemorrhage enrolled in an observational study. Readmission within 30 days was determined retrospectively by an automated query with manual confirmation. We identified the reason for readmission and tested for associations between readmission and functional outcomes using modified Rankin Scale (a validated functional outcome measure from 0, no symptoms, to 6, death) scores before intracerebral hemorrhage and at 14 days, 28 days, and 3 months after intracerebral hemorrhage. Setting:Neurologic ICU of a tertiary care hospital. Patients:Critically ill patients with spontaneous intracerebral hemorrhage. Interventions:Patients received standard critical care management for intracerebral hemorrhage. Measurements and Main Results:Of 246 patients (mean age, 65 yr; 51% female), 193 patients (78%) survived to discharge. Of these, 22 patients (11%) were readmitted at a median of 9 days (interquartile range, 4–15 d). The most common readmission diagnoses were infections after discharge (n = 10) and vascular events (n = 6). Age, history of stroke and hypertension, severity of neurologic deficit at admission, Acute Physiology and Chronic Health Evaluation score, ICU and hospital length of stay, ventilator-free days, days febrile, and surgical procedures were not predictors of readmission. History of coronary artery disease was associated with readmission (p = 0.03). Readmitted patients had similar modified Rankin Scale and severity of neurologic deficit at 14 days but higher (worse) modified Rankin Scale scores at 3 months (median [interquartile range], 5 [3–6] vs 3 [1–4]; p = 0.01). Conclusions:Severity of illness and hospital complications were not associated with 30-day readmission. The most common indication for readmission was infection after discharge, and readmission was associated with worse functional outcomes at 3 months. Preventing readmission after intracerebral hemorrhage may depend primarily on optimizing care after discharge and may improve functional outcomes at 3 months.

Frequency of acute changes found on head computed tomographies in critically ill patients: A retrospective cohort study☆☆☆★★★

PURPOSE The frequency of positive findings on computed tomography (CT) of the head in critically ill patients who develop neurologic dysfunction is not known. MATERIALS AND METHODS Cohort study of head CTs for patients admitted to 3 intensive care units from 2005 to 2010. We documented the frequency of acute changes for all head CTs and for the subgroup of patients with altered mental status (AMS). We also examined associations between patient characteristics or medications administered before head CT and the odds of an acute change on head CT using multivariate logistic regression. RESULTS During 11 338 intensive care unit admissions, there were 901 eligible head CTs on 706 patients (6% of patients). Among head CTs, 155 (17.2%) assessed concern of new focal deficit, 99 (11.0%) concern for a seizure, and 635 (70.5%) for AMS. Acute changes were found on 109 (12.1%; 95% confidence interval [CI], 10.0%-14.2%) of all head CTs, and 30% (22.4%-36.9%) of patients with focal deficits, 16.2% (8.8%-23.5%) of patients with seizures but only 7.4% (5.4%-9.4%) for patients with AMS. A diagnosis of sepsis was associated with a decreased odds of an acute change on head CT for all head CTs (odds ratio 0.61; 95% CI, 0.40-0.95; P = .028) but was not significantly associated with a decreased risk among the cohort of head CTs for AMS (odds ratio 0.82; 95% CI, 0.41-1.62; P = .56). No other factors were associated with an altered risk of acute change on head CT for all patients in our cohort or for those with AMS. CONCLUSIONS Acute changes on head CTs performed for concern regarding new focal neurologic deficit or seizures are frequent compared with those performed for AMS with a nonfocal examination. No specific patient characteristics or medications were associated with a large change in the likelihood of finding an acute change for patients with AMS.

Acute changes in ventricular volume during treatment for hepatic and renal failure.

Hepatic encephalopathy (HE) exists on a spectrum from minimal dysfunction to coma and may arise from ammonia-associated neurotoxicity whereby metabolic dysfunction leads to glutamine accumulation, astrocyte swelling, and nitric oxide–induced vasodilation.1 Elevated intracranial pressure (ICP), secondary to cerebral edema, is common in liver failure and occurs in 80% of comatose patients.1–3 Nonetheless, invasive ICP monitoring remains contentious in HE due to hemorrhagic complications and lack of evidence supporting benefit.3 A radiographic technique to assess edema could be helpful but head CT is only 33% sensitive for cerebral edema.2,3 We present a case illustrating this limitation of CT, the potential for rapid changes in cerebral edema, and a potential noninvasive means of assessing cerebral edema evolution.

Re: Confounding by Indication in Retrospective Studies of Intracerebral Hemorrhage: Antiepileptic Treatment and Mortality

To the Editor, We were interested to read the article by Battey and colleagues [1] regarding the analysis of datasets of patients with intracerebral hemorrhage (ICH). It is asserted that patients who survive at least 5 days are more suitable for analysis for the effect of seizure medications (now the preferred term [2]). This technique, however, is itself likely to lead to a biased dataset, and such a selection criterion is particularly inappropriate to evaluate seizure medications. The analysis does not take the duration of treatment or dose of seizure medications given into account, but it is likely to be important. One day of phenytoin (while a comatose patient undergoes EEG monitoring) is not likely to be the same as 14 days of phenytoin, which is why we took care to show that longer duration of treatment is associated with more complications in patients with ICH [2], and subsequent worse functional outcomes. More intense therapy is also associated with more complications and worse outcome in patients with subarachnoid hemorrhage [3]. Similar to the metric of pack-years for smoking exposure instead of a dichotomous one, analysis utilizing total dose exposure is important and fundamental to investigations of adverse drug effects. Furthermore, in this manuscript, seizure medications are grouped together, but each medication is likely to have a different safety profile and each may have a different effect on complications and outcomes. Five days after ICH symptom onset seems to be an arbitrary time to assess the impact of seizure medications. We [2] and others [4] have found that seizures after ICH usually occur within 24 h of symptom onset. Restricting the analysis to those who have survived at least 5 days will introduce bias by excluding patients most likely to have a seizure as a marker of disease, or who die as a consequence of seizures [5]. Mortality after ICH usually has a nonneurologic cause after a few days [6], so it is unclear why seizure medications should affect mortality. If one were to wait until 5 days after ICH symptom onset to randomize patients in a clinical trial of seizure medications, there would be relatively few events to study. The authors emphasize that their initial results suggested that seizure medications are lifesaving after ICH, and that only by selecting the subset of patients who had survived 5 days could they see that this was false. The initial results are a feint, however, since there is no established mechanism by which seizure medications would reduce mortality. Early clinical seizures are not independently associated with outcomes [4]. Seizure medications probably reduce mortality vs. placebo in patients with status epilepticus, but it is not clear from these data why such treatment should reduce mortality in an unselected cohort. We agree that patients who are prescribed seizure medications are likely to have more severe neurologic disease, but the authors neither present data on how the excluded patients might have differed from the overall dataset (i.e., might bias it) nor cite statistical literature that calls for excluding patients in this manner. The usual technique is to adjust the whole eligible cohort for A. M. Naidech (&) M. B. Maas E. M. Liotta J. C. Guth S. U. Schuele Departments of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA e-mail: a-naidech@northwestern.edu