Treatment of Hyponatremia in Patients with Acute Neurological Injury.

BACKGROUND: Little data exist regarding the practice of sodium management in acute neurologically injured patients. This study describes the practice variations, thresholds for treatment, and effectiveness of treatment in this population. METHODS: This retrospective, multicenter, observational study identified 400 ICU patients, from 17 centers, admitted for ≥48 h with subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), intraparenchymal hemorrhage, or intracranial tumors between January 1, 2011 and July 31, 2012. Data collection included demographics, APACHE II, Glascow Coma Score (GCS), serum sodium (Na+), fluid rate and tonicity, use of sodium-altering therapies, intensive care unit (ICU) and hospital length of stay, and modified Rankin score upon discharge. Data were collected for the first 21 days of ICU admission or ICU discharge, whichever came first. Sodium trigger for treatment defined as the Na+ value prior to treatment with response defined as an increase of ≥4 mEq/L at 24 h. RESULTS: Sodium-altering therapy was initiated in 34 % (137/400) of patients with 23 % (32/137) having Na+ >135 mEq/L at time of treatment initiation. The most common indications for treatment were declining serum Na+ (68/116, 59 %) and cerebral edema with mental status changes (21/116, 18 %). Median Na+ treatment trigger was 133 mEq/L (IQR 129-139) with no difference between diagnoses. Incidence and treatment of hyponatremia was more common in SAH and TBI [SAH (49/106, 46 %), TBI (39/97, 40 %), ICH (27/102, 26 %), tumor (22/95, 23 %); p = 0.001]. The most common initial treatment was hypertonic saline (85/137, 62 %), followed by oral sodium chloride tablets (42/137, 31 %) and fluid restriction (15/137, 11 %). Among treated patients, 60 % had a response at 24 h. Treated patients had lower admission GCS (12 vs. 14, p = 0.02) and higher APACHE II scores (12 vs. 10, p = 0.001). There was no statistically significant difference in outcome when comparing treated and untreated patients. CONCLUSION: Sodium-altering therapy is commonly employed among neurologically injured patients. Hypertonic saline infusions were used first line in more than half of treated patients with the majority having a positive response at 24 h. Further studies are needed to evaluate the impact of various treatments on patient outcomes.

Early pharmacological treatment of delirium may reduce physical restraint use: a retrospective study.

INTRODUCTION: Evidence surrounding pharmacological treatment of delirium is limited. The negative impact of physical restraints on patient outcomes in the intensive care unit (ICU), however, is well published. The objective of this study was to evaluate whether initiating pharmacologic delirium treatment within 24 hours of a positive screen reduces the number of days in physical restraints and improves patient outcomes compared with delayed or no treatment. METHODS: Patients from a mixed ICU with a documented positive delirium score using the Intensive Care Delirium Screening Checklist were retrospectively grouped based on having received pharmacologic treatment within 24 hours of the first positive screen or not. Primary end points were number of days spent in physical restraints and time to extubation after delirium onset. Secondary end points included hospital and ICU length of stay (LOS) and survival to discharge. RESULTS: Two hundred intubated patients were either pharmacologically treated (n = 98) or not treated (n = 102) within 24 hours of the first positive delirium score. Patients receiving treatment spent a shorter median time in restraints compared with patients who were not treated (3 vs 6 days; P < .001), and had a shorter median time to extubation (3 vs 6.5 days; P < .001). The treatment group also experienced a shorter ICU LOS (9.5 vs 16 days; P < .001) and hospital LOS (14.5 vs 22 days; P < .001) compared with the no-treatment group. CONCLUSIONS: Delirious patients who received pharmacological treatment within 24 hours of the first positive screen spent fewer days in physical restraints and less time receiving mechanical ventilation compared with those who did not. Although delirium management is multifactorial, early pharmacological therapy may benefit patients diagnosed with delirium.

High glucose variability increases cerebral infarction in patients with spontaneous subarachnoid hemorrhage.

PURPOSE: High glucose variability is a significant marker for poor outcome in critically ill patients. We evaluated the impact of high glucose variability on cerebral infarction following spontaneous subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Consecutive adult patients with spontaneous SAH and Hunt Hess score of at least 3 were retrospectively identified. Patients were excluded if their intensive care unit length of stay was less than 24 hours or if there were less than 5 glucose assessments. Glucose values from the first 7 days of intensive care unit admission were assessed. Variability was calculated as the average change in glucose over time for each patient. Classification and regression tree analysis was used to determine high vs low glucose variability, and the incidence of cerebral infarction was compared. Multivariate analysis was used to control for confounding variables. RESULTS: There were 42 patients. Classification and regression tree analysis revealed a change in glucose greater than 9.52 mg/dL/h as the determinant for high variability. The incidence of cerebral infarction was 64% when glucose variability was high vs 20% when it was low (P=.006). Multivariate analysis identified high glucose variability (odds ratio [95% confidence interval]=11.4 [1.9-70.2], P=.008) and female sex (odds ratio [95% confidence interval]=5.2 [1-26.8], P=.047) as independent predictors for cerebral infarction. CONCLUSION: Glucose variability is a significant predictor of cerebral infarction in patients with severe spontaneous SAH.

The first 72 hours of brain tissue oxygenation predicts patient survival with traumatic brain injury.

BACKGROUND: Utilization of brain tissue oxygenation (pBtO(2)) is an important but controversial variable in the treatment of traumatic brain injury. We hypothesize that pBtO(2) values over the first 72 hours of monitoring are predictive of mortality. METHODS: Consecutive, adult patients with severe traumatic brain injury and pBtO(2) monitors were retrospectively identified. Time-indexed measurements of pBtO(2), cerebral perfusion pressure (CPP), and intracranial pressure (ICP) were collected, and average values over 4-hour blocks were determined. Patients were stratified according to survival, and repeated measures analysis of variance was used to compare pBtO(2), CPP, and ICP. The pBtO(2) threshold most predictive for survival was determined. RESULTS: There were 8,759 time-indexed data points in 32 patients. The mean age was 39 years ± 16.5 years, injury severity score was 27.7 ± 10.7, and Glasgow Coma Scale score was 6.6 ± 3.4. Survival was 68%. Survivors consistently demonstrated higher pBtO(2) values compared with nonsurvivors including age as a covariate (F = 12.898, p < 0.001). Individual pBtO(2) was higher at the time points 8 hours, 12 hours, 20 hours to 44 hours, 52 hours to 60 hours, and 72 hours of monitoring (p < 0.05). There was no difference in ICP (F = 1.690, p = 0.204) and CPP (F = 0.764, p = 0.389) values between survivors and nonsurvivors including age as a covariate. Classification and regression tree analysis identified 29 mm Hg as the threshold at which pBtO(2) was most predictive for mortality. CONCLUSION: The first 72 hours of pBtO(2) neurologic monitoring predicts mortality. When the pBtO(2) monitor remains below 29 mm Hg in the first 72 hours of monitoring, mortality is increased. This study challenges the brain oxygenation threshold of 20 mm Hg that has been used conventionally and delineates a time for monitoring pBtO(2) that is predictive of outcome. LEVEL OF EVIDENCE: III, prognostic study.

Practice variations in the management of status epilepticus.

BACKGROUND: Numerous anticonvulsant agents are now available for treating status epilepticus (SE). However, a paucity of data is available to guide clinicians in the initial treatment of seizures or SE. This study describes the current strategies being employed to treat SE in the U.S.A. METHODS: Fifteen American academic medical centers completed a retrospective, multicenter, observational study by reviewing 10-20 of the most recent cases of SE at their institution prior to December 31, 2009. A multivariate analysis was performed to determine factors associated with cessation of seizures. RESULTS: A total of 150 patients were included. Most patients with SE had a seizure disorder (58%). SE patients required a median of 3 AEDs for treatment. Three quarters of patients received a benzodiazepine as first-line therapy (74.7%). Phenytoin (33.3%) and levetiracetam (10%) were commonly used as the second AED. Continuous infusions of propofol, barbiturate, or benzodiazepine were used in 36% of patients. Median time to resolution of SE was 1 day and was positively associated with presence of a complex partial seizure, AED non-compliance prior to admission, and lorazepam plus another AED as initial therapy. Prolonged ICU length of stay and topiramate therapy prior to admission were negatively associated with SE resolution. Mortality was higher in patients without a history of seizure (22.2 vs. 6.9%, p = 0.006). CONCLUSIONS: The use of a benzodiazepine followed by an AED, such as phenytoin or levetiracetam, is common as first and second-line therapy for SE and appears to be associated with a shorter time to SE resolution. AED selection thereafter is highly variable. Patients without a history of seizure who develop SE had a higher mortality rate.

Retrospective evaluation of nicardipine versus labetalol for blood pressure control in aneurysmal subarachnoid hemorrhage.

BACKGROUND: American Heart Association/American Stroke Association guidelines for management of aneurysmal subarachnoid hemorrhage (aSAH) recommend blood pressure (BP) control, utilizing labetalol or nicardipine, but do not differentiate efficacy between the two agents. The purpose of this retrospective study was to compare BP control between labetalol and nicardipine in patients following aSAH. METHODS: Consecutive adult patients admitted to the ICU with a diagnosis of SAH treated with labetalol or nicardipine were retrospectively identified. Patients were included if they received more than one bolus dose of labetalol or a nicardipine infusion for greater than 3 h. Patients were excluded if they were <18 years of age, experiencing an ICH, acute ischemic stroke or a TIA. Patients were stratified into two groups (labetalol vs. nicardipine) and data was collected for 72 h. The outcomes compared were time within goal mean arterial pressure (MAP), average MAP/patient, MAP variability, initial response to therapy, and treatment failure. Goal MAP was defined as 70-110 mmHg. RESULTS: There were 103 patients evaluated (labetalol n = 43; nicardipine n = 60). Demographics and baseline MAP were similar between the two groups. Nicardipine was associated with a longer time within goal MAP (78 ± 24 vs. 58 ± 36 %, p = 0.001) and lower average MAP/patient (93 ± 11 vs. 106 ± 12 mmHg, p < 0.001). There was no difference in MAP variability between the nicardipine and labetalol groups (13 ± 5 mmHg vs. 11 ± 4 mmHg; p = 0.137). Nicardipine led to a more rapid response to therapy (F = 8.1; p = 0.005) and fewer treatment failures (0 vs. 28 %, p < 0.001). CONCLUSIONS: Our study showed nicardipine to be associated with superior BP control versus labetalol in aSAH.

Adrenal insufficiency in cardiothoracic patients: an evaluation of the corticotrophin stimulation test and other diagnostic methods.

PURPOSE: The purposes of the study were to determine the incidence of adrenal insufficiency (AI) using several published techniques, compare the response rates using a low-dose (LD) corticotropin (ACTH) stimulation test vs a standard dose (SD), and identify the technique that is most closely related to vasopressor use. MATERIALS AND METHODS: Consecutive adult patients who were undergoing open heart surgery for CAD or valvular disease were prospectively enrolled. Exclusion criteria included history of steroid use, operative steroid, or etomidate administration. Postoperatively, each patient underwent ACTH stimulation with 1 µg (LD) and 249 µg (SD), 60 minutes apart. Agreement among the tests was evaluated, and vasopressor use was compared between groups. RESULTS: There were 40 patients evaluated. The incidence of AI based on operative change, postoperative values, and LD-ACTH and SD-ACTH tests was 53%, 38%, 60%, and 38%, respectively. Agreement between the LD- and SD-ACTH tests was 73% (κ = 0.476, P = .001). There was a significant difference in the need for (93% vs 52%, P = .013) and duration (18.9 [0-180.6] vs 0.6 [0-73.2] hours, P = .003) of vasopressor therapy in patients with and without AI but only using the SD-ACTH definition. CONCLUSION: The incidence of AI will vary greatly based on technique used for diagnosis. The SD-ACTH stimulation test should be used to determine AI in open heart patients postoperatively because of the close association with vasopressor usage.

Cerebral perfusion pressure and intracranial pressure are not surrogates for brain tissue oxygenation in traumatic brain injury.

OBJECTIVE: Utilization of brain tissue oxygenation (pBtO(2)) is an important but controversial variable in the treatment of traumatic brain injury (TBI). We evaluated the correlation between pBtO(2)/CPP and pBtO(2)/ICP and determined the parameter most closely related to survival. METHODS: Consecutive, adult patients with severe TBI and pBtO(2) monitors were retrospectively identified. Time-indexed measurements of pBtO(2), CPP and ICP were collected and correlation coefficients were determined. Patients were then stratified according to survival and pBtO(2), CPP and ICP values were compared between groups. RESULTS: There were 4169 time-indexed data points (i.e., pBtO(2) with respective CPP and ICP values) in 15 patients. The cohort consisted of a mean age of 37±17 years, ISS of 27±7 and GCS of 4.5±1.5. Survival was 53% (8/15). In a normal regression models, neither the ICP (p=0.58) nor the CPP (p=0.71) predict pBtO(2) significantly. There was a significant difference in pBtO(2) in survivors (31.5±3.1 vs. 25.2±4.8, p=0.010) but not in CPP or ICP. Survivors had a lower proportion of time with pBtO(2)<25 mmHg [20% (3.4-44.6) vs. 40% (16.2-89), p=0.049]. In contrast, survivors had a greater proportion of time with CPP<70 and no difference in the proportion of time with and ICP>20. CONCLUSIONS: CPP and ICP should not be used as surrogates for pBtO(2) since cerebral oxygenation varies independently of cerebral hemodynamics and pressures. Brain tissue oxygen monitoring in patients with TBI provides unique information regarding cerebral oxygenation the utility of which remains to be fully described. SIGNIFICANCE: CPP and ICP are not surrogates for pBtO(2). Brain tissue oxygenation monitoring provides unique information for the treatment of traumatically injured patients.

The effect of a computer-assisted insulin protocol on glycemic control in a surgical intensive care unit.

BACKGROUND: Computer-assisted insulin protocols (CAIPs) contain complex mathematical algorithms to assist with insulin dosing. This study compared the quality of glucose control utilizing a CAIP with a paper-based insulin protocol (PBIP). METHODS: This before-after study identified consecutive patients who received continuous insulin therapy for at least 24 h. Patients were stratified into two groups (PBIP and CAIP). The target blood glucose range for both was 80-110 mg/dL. Hypoglycemia was defined as the percentage of patients with any glucose value <40 mg/dL. Variability was measured by reporting the SD for each patients mean glucose value. RESULTS: There were 192 patients evaluated (PBIP, n = 145; CAIP, n = 47). More glucose readings were within target range using the CAIP protocol (49 ± 14% vs. 40 ± 12%, P < 0.001), but no difference in mean glucose was noted (113 ± 11 mg/dL with CAIP vs. 116 ± 11 mg/dL with PBIP, P = 0.067). The incidence of hypoglycemia was similar between the CAIP and PBIP groups, respectively (2.1% vs. 4.1%, P = 0.518). Glucose variability was lower with the CAIP (25 ± 9 mg/dL vs. 31 ± 11 mg/dL, P = 0.001). The CAIP required more frequent blood glucose assessments (16 ± 2 vs. 12 ± 2 per day, P < 0.001), more insulin dosing adjustments (14 ± 3 vs. 5 ± 2 per day, P < 0.001), and more time per day (84 ± 15 vs. 51 ± 8 min per patient, P < 0.001) compared with the PBIP. CONCLUSIONS: A CAIP will lead to minor improvements in glucose control and decrease glucose variability but will not change the rate of hypoglycemia or response to insulin therapy. These differences could largely be due to more aggressive monitoring and titrations required by a CAIP.

Adverse drug reactions resulting in hyperthermia in the intensive care unit.

Hyperthermia is frequently seen in the intensive care setting and is associated with significant morbidity and mortality. It is often initially misdiagnosed as fever associated with infection. Atypical presentations of classic syndromes are common. Clinical suspicion is the key to diagnosis. Adverse drug reactions are a frequent culprit. Syndromes include adrenergic "fever," anticholinergic "fever," antidopaminergic "fever," serotonin syndrome, malignant hyperthermia, uncoupling of oxidative phosphorylation, and withdrawal from baclofen. This review describes the pathophysiology of hyperthermia, as distinct from fever, and the physiology, diagnosis, and treatment of serotonin syndrome, neuroleptic malignant syndrome, malignant hyperthermia, and baclofen withdrawal. Much of the available evidence regarding the treatment of these disorders is based on single case reports, case series, or animal models. Therapeutic modalities consist of identification/withdrawal of possible offending agent(s), support directed at lowering temperature and preventing/treating complications, as well as targeted pharmacologic therapy directed at the specific cause. Early recognition and treatment using a multidisciplinary approach are essential to achieve the best possible outcome.

Current and future treatment considerations in the management of aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a type of hemorrhagic stroke that can cause significant morbidity and mortality. Although guidelines have been published to help direct the care of these patients, there is insufficient quality literature regarding the medical and pharmacological management of patients with aSAH. Treatment is divided into 3 categories: supportive therapy, prevention of complications, and treatment of complications. There are numerous pharmacological therapies that are targeted at prevention and treatment of the neurological and medical complications that may arise. Rebleeding, hydrocephalus, cerebral vasospasm, and seizures are the most common neurological complications while the most common medical complications include hyponatremia, pulmonary edema, cardiac arrhythmias, neurogenic stunned myocardium, fever, anemia, infection, hyperglycemia, and venous thromboembolism. Risk factors, clinical presentation, diagnosis, pathophysiology, as well as initial management, prevention, and treatment of complications will be the focus of this discussion.

Impact of dexmedetomidine on analgesic requirements in patients after cardiac surgery in a fast-track recovery room setting.

STUDY OBJECTIVE: To compare postoperative opioid requirements in patients who received dexmedetomidine versus propofol after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Large, community teaching hospital that uses a fast-track cardiovascular recovery unit (CVRU) model. PATIENTS: One hundred adults who underwent coronary artery bypass graft surgery and/or valvular surgery, and who received either dexmedetomidine (50 patients) or propofol (50 patients) for perioperative sedation. MEASUREMENTS AND MAIN RESULTS: Patients were matched according to surgery type and left ventricular ejection fraction. Opioid requirements were assessed over two time intervals: from arrival in the CVRU to discontinuation of the sedative infusion, and from CVRU arrival to CVRU discharge, up to a maximum of 72 hours if admission to the intensive care unit was necessary. All postoperative opioid doses were converted to morphine equivalents. Length of mechanical ventilation, quality of sedation, adverse drug events, and sedation-related costs were determined. Opioid requirements were significantly lower during the sedative infusion period for dexmedetomidine-treated patients than for propofol-treated patients (median [range] 0 [0-10 mg] vs 4 mg [0-33 mg], p<0.001), but not through the entire CVRU admission (median [range] 26 mg [0-119 mg] vs 30 mg (0-100 mg], p=0.284). The proportion of patients who did not require opioids during the infusion was significantly higher in the dexmedetomidine group compared with the propofol group (32 [64%] vs 13 [26%], p<0.001). No significant differences were noted between the groups for length of mechanical ventilation, quality of sedation, or adverse events. Sedation-related costs were significantly higher (approximately $50/patient higher) with dexmedetomidine (p<0.001). CONCLUSION: Dexmedetomidine resulted in lower opioid requirements in patients after cardiac surgery versus those receiving propofol, but this did not result in shorter durations of mechanical ventilation, using a fast-track CVRU model.

Mechanical prophylaxis to prevent venous thromboembolism in surgical patients: a prospective trial evaluating compliance.

PURPOSE: Sequential compression devices (SCDs) and venous foot pumps (VFPs) are used to prevent venous thromboembolism in surgical patients, but compliance is presumed to be poor. We evaluated compliance with these devices, compared compliance between intensive care unit (ICU) and non-ICU patients, and identified factors associated with better compliance. MATERIALS AND METHODS: Compliance was prospectively evaluated twice daily from admission until discharge, ambulation, or device discontinuation. A compliance score was determined by dividing the number of compliant evaluations by the total number of assessments. Compliance was compared between ICU and non-ICU patients, and predictors for compliance were identified. RESULTS: There were 150 patients evaluated. Overall compliance was 73 +/- 29. Compliance was higher in ICU patients compared to non-ICU patients (82 +/- 22 vs 62 +/- 32; P < .001). Admission to the ICU (odds ratio [OR], 2.21 [1.04-4.65]; P = .038) and SCD use (as opposed to VFP) (OR, 2.94 [1.36-6.37]; P = .006) were independent predictors for better compliance. CONCLUSIONS: Compliance with mechanical prophylaxis is suboptimal particularly in non-ICU patients. Strategies to improve compliance or alternative prophylaxis should be considered in those patients.

Limitations of a standardized weight-based nomogram for heparin dosing in patients with morbid obesity.

BACKGROUND: Confusion exists when dosing heparin using a weight-based nomogram in the obese population. At 2 affiliated community teaching hospitals, we compared the activated partial thromboplastin time (aPTT) values in morbidly obese and nonmorbidly obese patients using a standardized nomogram and determined factors associated with achieving a supratherapeutic aPTT value. METHODS: This was a retrospective study that included patients who had received intravenous heparin according to a standardized weight-based nomogram for >or=12 hours. The exclusion criteria were age <18 years, pregnancy, and insufficient data. Patients were stratified into morbidly obese (body mass index [BMI] >or=40 kg/m(2)) and nonmorbidly obese (BMI <40 kg/m(2)) groups. The aPTT values were compared and predictors for a supratherapeutic aPTT values were identified. RESULTS: A total of 101 patients were included in the study. Greater aPTT values were noted at 6 hours (155 +/- 37 versus 135 +/- 44, P = .020) and 12 hours (141 +/- 45 versus 117 +/- 45, P = .012) for patients with morbid obesity than for those without it, respectively. Increasing BMI (odds ratio = 1.06, 95% confidence interval 1.02-1.1; P = .003) and age (odds ratio 1.05, 95% confidence interval 1.02-.09; P = .001] were independent predictors of supratherapeutic aPTT values. CONCLUSION: Heparin dosing with a weight-based nomogram will yield greater aPTT values in morbidly obese patients. Consideration of BMI and age can help identify those patients at risk of supratherapeutic aPTTs. Alternative strategies, such as a dose cap should be considered in patients with morbid obesity.

Medication reconciliation effect on prolonged inpatient stress ulcer prophylaxis.

BACKGROUND: While medication reconciliation (MR) has been shown to reduce medication errors by limiting errors of transcription, omission, and duplicate therapy, its impact on the provision of unnecessary prophylaxis is largely unknown. OBJECTIVE: To determine the effect of MR on the incidence of prolonged stress ulcer prophylaxis (SUP) across the continuum of care from hospital admission to discharge as well as evaluate clinical conditions associated with prolonged SUP. METHODS: This retrospective study assessed patients who were admitted to the intensive care unit (ICU) and had SUP initiated. Patients were excluded if they were receiving gastroprotective therapy prior to ICU admission, were being treated for an acute gastrointestinal hemorrhage, or died. The need for SUP was determined using risk factors adapted from evidence-based guidelines developed by the American Society of Health-System Pharmacists. The use of SUP was assessed upon transfer from the ICU to a non-ICU setting and at hospital discharge. Results were compared between pre-MR and post-MR groups. RESULTS: Data from 114 (pre-MR, n = 53; post-MR, n = 61) medical and surgical ICU patients were evaluated. There was no significant difference in the use of prolonged SUP upon transfer from the ICU to a non-ICU setting in the pre-MR and post-MR groups, respectively (85% [45/53] vs 79% [48/61], p = 0.393). Similarly, there was no significant difference in the use of prolonged SUP upon hospital discharge in the pre-MR and post-MR groups, respectively (14% [6/44] vs 23% [10/43], p = 0.247). There were no clinical conditions for which prolonged SUP use was predominant. CONCLUSIONS: The strategy of MR alone will not decrease the incidence of prolonged SUP in hospitalized patients. Other techniques should be evaluated to encourage appropriate use of acid-suppressive agents.