Insulin Glargine in Critically ill Patients: Once/Day versus Twice/Day Dosing.

OBJECTIVE: Twice/day dosing of insulin glargine has been used to treat hyperglycemia in clinical practice; however, data supporting its use in the critically ill population are lacking. This study was designed to evaluate the safety and efficacy of twice/day insulin glargine in critically ill patients. METHODS: A retrospective study was conducted in adult patients admitted to the intensive care units between February 2013 and June 2017 who received insulin glargine twice/day or 40 units or more once/day for 48 hours or longer. Post cardiovascular surgery patients were excluded. Data were collected for up to 14 patient-days. The efficacy outcomes included the incidence of hyperglycemia (blood glucose [BG] above 180 mg/dl), predose hyperglycemia rate (BG above 180 mg/dl within 4 hrs before the dose), and BG variability (standard deviation). The safety outcome was assessed by the development of hypoglycemia (BG below 70 mg/dl). RESULTS: A total of 58 patients (twice/day = 23; once/day = 35) were included in the analysis. Demographics were similar between the groups including history of diabetes mellitus, baseline hemoglobin A1C , and home insulin use. No difference was observed between the twice/day and once/day groups in the mean BG (153 vs 154 mg/dl, p=0.95, respectively), and BG variability (46 vs 44 mg/dl, p=0.29, respectively). Although the overall incidence of hyperglycemia was similar between twice/day and once/day groups (96% vs 97%, p=1.00, respectively), the twice/day group had a significantly lower predose hyperglycemia rate (twice/day 0.27 vs once/day 0.43, p=0.02). Additionally, the twice/day group did not experience an increased incidence of hypoglycemia (twice/day 23% vs once/day 34%, p=0.57) or hypoglycemia without having anything by mouth (twice/day 0% vs once/day 9%, p=0.27). CONCLUSIONS: This is the first study demonstrating that twice/day insulin glargine reduced the rate of predose hyperglycemia without increasing the risk of hypoglycemia in critically ill patients. A large randomized study is needed to confirm the safety and efficacy of twice/day glargine in the critically ill.

Hypocalcemia in trauma patients receiving massive transfusion.

BACKGROUND: Massive transfusion protocol (MTP) is increasingly used in civilian trauma resuscitation. Calcium is vital for coagulation, but hypocalcemia commonly occurs during massive transfusion due to citrate and serum calcium chelation. This study was conducted to determine the incidence of hypocalcemia and severe hypocalcemia in trauma patients who receive massive transfusion and to compare characteristics of patients with severe versus nonsevere hypocalcemia. MATERIALS AND METHODS: This was a retrospective study of trauma patients who received massive transfusion between January 2009 and November 2013. The primary outcome was the incidence of hypocalcemia (ionized calcium [iCa] < 1.12 mmol/L) and severe hypocalcemia (iCa < 0.90 mmol/L). Secondary outcomes included calcium monitoring, calcium replacement, and correction of coagulopathy. RESULTS: There were 156 patients included; 152 (97%) experienced hypocalcemia, and 111 (71%) had severe hypocalcemia. Patients were stratified into iCa ≥ 0.90 (n = 45) and iCa < 0.90 (n = 111). There were no differences in demographics or baseline laboratories except the severe hypocalcemia group had higher baseline activated partial thromboplastin time (29.7 [23.7-50.9] versus 25.8 [22.3-35.9], P = 0.003), higher lactic acid (5.8 [4.1-9.8] versus 4.0 [3.1-7.8], P = 0.019), lower platelets (176 [108-237] versus 208 [169-272], P = 0.003), and lower pH (7.14 [6.98-7.28] versus 7.23 [7.14-7.33], P = 0.019). Mortality was higher in the severe hypocalcemia group (49% versus 24%, P = 0.007). Patients in the iCa < 0.90 group received more blood products (34 [23-58] versus 22 [18-30] units, P < 0.001), and calcium chloride (4 [2-7] versus 3 [1-4] g, P = 0.002), but there was no difference in duration of MTP or final iCa. Neither group reached a median iCa > 1.12. CONCLUSIONS: Hypocalcemia is common during MTP, and vigilant monitoring is warranted. Research is needed to effectively manage hypocalcemia during massive transfusion.

Prophylaxis of Venous Thrombosis in Neurocritical Care Patients: An Evidence-Based Guideline: A Statement for Healthcare Professionals from the Neurocritical Care Society.

The risk of death from venous thromboembolism (VTE) is high in intensive care unit patients with neurological diagnoses. This is due to an increased risk of venous stasis secondary to paralysis as well as an increased prevalence of underlying pathologies that cause endothelial activation and create an increased risk of embolus formation. In many of these diseases, there is an associated risk from bleeding because of standard VTE prophylaxis. There is a paucity of prospective studies examining different VTE prophylaxis strategies in the neurologically ill. The lack of a solid evidentiary base has posed challenges for the establishment of consistent and evidence-based clinical practice standards. In response to this need for guidance, the Neurocritical Care Society set out to develop and evidence-based guideline using GRADE to safely reduce VTE and its associated complications.

Hyponatremia in Patients with Spontaneous Intracerebral Hemorrhage.

Hyponatremia is the most frequently encountered electrolyte abnormality in critically ill patients. Hyponatremia on admission has been identified as an independent predictor of in-hospital mortality in patients with spontaneous intracerebral hemorrhage (sICH). However, the incidence and etiology of hyponatremia (HN) during hospitalization in a neurointensive care unit following spontaneous intracerebral hemorrhage (sICH) remains unknown. This was a retrospective analysis of consecutive patients admitted to Detroit Receiving Hospital for sICH between January 2006 and July 2009. All serum Na levels were recorded for patients during the ICU stay. HN was defined as Na <135 mmol/L. A total of 99 patients were analyzed with HN developing in 24% of sICH patients. Patients with HN had an average sodium nadir of 130 ± 3 mmol/L and an average time from admission to sodium <135 mmol/L of 3.9 ± 5.7 days. The most common cause of hyponatremia was syndrome of inappropriate antidiuretic hormone (90% of HN patients). Patients with HN were more likely to have fever (50% vs. 23%; p = 0.01), infection (58% vs. 28%; p = 0.007) as well as a longer hospital length of stay (14 (8-25) vs. 6 (3-9) days; p < 0.001). Of the patients who developed HN, fifteen (62.5%) patients developed HN in the first week following sICH. This shows HN has a fairly high incidence following sICH. The presence of HN is associated with longer hospital length of stays and higher rates of patient complications, which may result in worse patient outcomes. Further study is necessary to characterize the clinical relevance and treatment of HN in this population.

A prospective evaluation of labetalol versus nicardipine for blood pressure management in patients with acute stroke.

INTRODUCTION: Acute hypertension is common following stroke and contributes to poor outcomes. Labetalol and nicardipine are often used for acute hypertension but there are little data comparing the two. This study is to evaluate the therapeutic response and tolerability of these two agents following acute stroke. METHODS: This is a prospective, pseudo-randomized study comparing labetalol and nicardipine for blood pressure (BP) management in acute stroke patients. Patients who presented to the emergency department (ED) with confirmed hemorrhagic or ischemic stroke received either labetalol or nicardipine for 24 h from ED admission. Therapeutic response was assessed by achievement of goal BP, time spent within goal, and variability in BP. Clinical outcomes including length of stay, clinical status at discharge, and in-hospital mortality were recorded. RESULTS: 54 patients were enrolled (labetalol = 28; nicardipine = 26) with 25 ± 6 BP measurements per patient. Majority of patients had a hemorrhagic stroke and baseline characteristics were similar between groups. All patients who received nicardipine achieved goal BP compared to 17 (61 %) in the labetalol group (p < 0.001) with 89 % nicardipine-treated patients achieved goal BP within 60 min of drug initiation versus 25 % in labetalol group (p < 0.001). Nicardipine group had better maintenance of BP, a greater percentage of time spent within goal, and significantly less BP variability compared to labetalol group (p < 0.001). Less rescue antihypertensive agents were given to nicardipine group than labetalol group (p < 0.001). The incidences of adverse drug events were similar between groups and there were no differences in clinical outcomes. CONCLUSION: In acutely hypertensive stroke patients, superior therapeutic response was achieved with nicardipine versus labetalol. Despite this, there was no demonstrable difference in clinical outcomes.

Measures to improve safety of an elastomeric infusion system for pain management.

PURPOSE: Measures to improve the safe implementation and utilization of an elastomeric infusion system for pain management are described. SUMMARY: Due to the multiple safety concerns associated with the use of the On-Q infusion systems (I-Flow Corporation, Lake Forest, CA) in a community-based teaching institution, a multidisciplinary team of physicians, pharmacists, clinical nurses, nurse educators, and computer informatics personnel was formed to develop a standardized policy and procedure to ensure the safe use of On-Q pumps. The policy addressed several problems concerning prescribing, dispensing, administration, and monitoring of these pumps. The patient care policy for use of On-Q pumps dictates how the pumps are stocked, ordered, dispensed, administered, and monitored and the drugs approved for use in the pumps. Education bulletins, a summary of the new policy and procedure, and a formal presentation of the policy and procedure to unit-based nurse educators were provided. The focus was on a consistent message of safety by reiterating the problems described with these pumps in the literature and in the health care system itself. The physicians ordering the devices have provided positive feedback regarding the simplified ordering process and standardization of the pumps, medications, and concentrations. Both dispensing pharmacists and bedside nurses have noted that the orders are clearly communicated via the computerized system. The addition of documentation in the computer system and education regarding potential signs and symptoms of adverse events with the medication used with the pumps was greatly appreciated by the nursing staff. CONCLUSION: A health care system instituted measures to enhance the safety of using an elastomeric infusion system for pain management.

Medical management of variceal hemorrhage.

Gastroesophageal variceal hemorrhage is a major complication of portal hypertension in 50% to 60% of patients with liver cirrhosis and is a frequent cause of mortality in these patients. The prevalence of variceal hemorrhage is approximately 5% to 15% yearly, and early variceal rebleeding has a rate of occurrence of 30% to 40% within the first 6 weeks. More than 50% of patients who survive after the first bleeding episode will experience recurrent bleeding within 1 year. Management of gastroesophageal varices should include prevention of initial and recurrent bleeding episodes and control of active hemorrhage. Therapies used in the management of gastroesophageal variceal hemorrhage may include pharmacologic therapy (vasoactive agents, nonselective b-blockers, and antibiotic prophylaxis), endoscopic therapy, transjugular intrahepatic portosystemic shunt, and shunt surgery. This article focuses primarily on pharmacologic management of acute variceal hemorrhage.

Management of spontaneous nontraumatic intracranial hemorrhage.

Intracerebral hemorrhage (ICH) is one of the most devastating subtypes of stroke and is characterized by spontaneous extravasation into the parenchymal tissue of the brain. Although advances in critical care have improved, there is no intervention currently available that has shown to alter the outcome of patients who have suffered acute ICH. Therefore, management is largely supportive. Treatment strategies are aimed at limiting hematoma enlargement, seizures, and cerebral edema, as well as other ICU-related complications such as deep venous thrombosis, hyperglycemia, and fever. This review will outline the key pharmacological management strategies in patients with ICH and highlight the most current American Heart Association/American Stroke Association (AHA/ASA) guidelines for management published in 2007.

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.

Temperature management in acute neurologic injury: to cool or not to cool.

Therapeutic hypothermia is becoming an important intervention following acute neurologic injury despite inconclusive results concerning efficacy. This enthusiasm primarily stems from a lack of other effective interventions in this population. With the increase in the use of therapeutic hypothermia, several practical issues must be considered when initiating this intervention. Clinical pharmacists can play an important role in anticipating and addressing some complications such as shivering, slow drug metabolism, and infection. This review will discuss the available literature concerning the efficacy of therapeutic hypothermia in various neurologic injuries, as well as the most common adverse events associated with it.

Possible removal of topiramate by continuous renal replacement therapy.

BACKGROUND: Topiramate is primarily renally eliminated and requires dosage adjustment based upon renal function. While there is data to suggest drug removal during intermittent hemodialysis (IHD), little is known regarding its clearance and dosing during continuous renal replacement therapy (CRRT). CASE DESCRIPTION: We describe a 59-year-old man with refractory status epilepticus who was started on continuous venovenous hemodiafiltration (CVVHDF) for acute renal failure while receiving topiramate with a series of serum concentrations to assess for removal during CVVHDF. CONCLUSION: Our data suggest clinically important amounts of topiramate are removed by CRRT, and higher topiramate dosage may be needed for these patients instead of the current recommended 50% of normal dosage. Unfortunately, there is no antiepileptic drug dosing recommendation when used during CRRT due to the paucity of data. This case highlights a need for research evaluating the effect of CRRT on AED elimination in order to optimize therapy for seizure control.

Clinical impact of early hyperglycemia during acute phase of traumatic brain injury.

INTRODUCTION: While tight glucose control has been widely adopted in the critical care setting, the optimal target glucose level following acute traumatic brain injury (TBI) remains debatable. This observational study was conducted to delineate the relationship between glucose levels and clinical outcomes during acute phase (first 5 days) of TBI. METHODS: We retrospectively identified 429 TBI patients admitted to the intensive care unit (ICU) from January 2005 to December 2006. Of those, 380 patients were retained for final analysis. Collected data included demographics, admission Glasgow Coma Scale (GCS), and APACHE II, glucose on admission and during the first 5 days of admission, and insulin use. Clinical outcomes included mortality, ICU, and hospital length of stay. RESULTS: The overall hospital mortality was 13.2% (n = 50). Demographics were similar between survivor and nonsurvivor groups; however, nonsurvivors were older and had worse disease severity on admission. Nonsurvivors also had significantly higher glucose levels at admission and during the first 24 h of admission (P < 0.001). Based on the receiver operating characteristic (ROC) curve, admission and day-1 peak glucose were better predictors for mortality compared to hospital days 2-5 glucose levels, with day-1 peak glucose being the best predictor of mortality (AUC = 0.820). A Kaplan-Meier survival analysis also showed that patients with glucose <160 mg/dl during the first day of ICU admission had a significantly better survival rate compared to those with glucose > or =160 mg/dl (P < 0.001). Two glucose bands, <60 and > or =160 mg/dl, were identified to be associated with increased mortality irrespective of injury severity (OR = 1.130; 95% CI 1.034-1.235; P = 0.007; OR = 1.034; 95% CI 1.021-1.047, P < 0.001; respectively). CONCLUSIONS: Findings from our study suggest a glucose level > or =160 mg/dl within the first 24 h of admission following TBI is associated with poor outcomes irrespective of severity of injury, and this presents a timeframe for which active therapeutic interventions may improve clinical outcomes. Prospective efficacy trials are needed to corroborate these findings.

Role of hypertonic saline for the management of intracranial hypertension after stroke and traumatic brain injury.

Increased intracranial pressure after neurologic injury is a clinical challenge that often requires administration of osmotic agents. The most common osmotic agent used for treatment has been mannitol; however, interest has been renewed in using hypertonic saline after neurologic injury, since it is not associated with hypovolemia. The types of procedures or injury for which hypertonic saline has been used are vast, from elective craniotomy for tumor resection to stroke and traumatic brain injury. Unfortunately, there is a paucity of well-controlled clinical trials that provide evidence for the best concentration, administration approach, and length of therapy with hypertonic saline. The bulk of the data exists for traumatic brain injury, although most of these data are from observational and retrospective analyses, which do not allow for an evaluation of the impact of hypertonic saline on clinical outcomes. Nonetheless, both animal and clinical data suggest that patients with traumatic brain injury and those with stroke may benefit from hypertonic saline therapy. Since hypertonic saline has a high risk of injury with inappropriate administration and is considered a "high-alert" drug, safety issues surrounding its dispensing and administration must be considered. Randomized outcome trials comparing mannitol with hypertonic saline in various subpopulations of neurologic injury would add valuable information to the literature and provide a basis for establishment of best clinical practices.

Hemostatic therapy for the treatment of intracranial hemorrhage.

Intracranial hemorrhage results in poor neurologic outcomes and high mortality. Current management is limited to supportive care. In addition to the initial bleeding event, rebleeding and hematoma expansion have been identified as major risk factors for poor outcomes in these patients. The antifibrinolytic agents tranexamic acid, aminocaproic acid, and recombinant activated factor VII (rFVIIa) have been studied with the hopes of achieving early hemostasis and improving outcomes. Available data suggest that tranexamic acid and aminocaproic acid are more harmful than beneficial for this indication; therefore, they have no role in the treatment of intracranial bleeding. Alternatively, rFVIIa, has shown promising results in the management of spontaneous intracerebral hemorrhage. Clinicians should be aware of the available evidence regarding the use of these hemostatic agents in the management of intracranial hemorrhage, including traumatic brain injury, intracerebral hemorrhage, and subarachnoid hemorrhage.

A comparison of nicardipine and labetalol for acute hypertension management following stroke.

OBJECTIVE: Evaluate the ease of use and tolerability of labetalol (L) and nicardipine (N) for hypertension management in patients with acute stroke. METHODS: This is a retrospective, non-randomized study. Consecutive adults within 24 h of hospital admission who received intravenous bolus labetalol or nicardipine infusion as first-line antihypertensive therapy were identified. Hemodynamic data were collected through 24 h of therapy. RESULTS: Ninety patients received either labetalol (N = 64) or nicardipine (N = 26) initially for blood pressure (BP) management. Stroke types were 54% intracerebral hemorrhage (ICH), 22% subarachnoid hemorrhage, and 23% ischemic stroke and were similar between the two drug groups. Baseline patient characteristics and disease severity (APACHE II and GCS) were similar between groups. The average total daily labetalol dose was 40 (10-340) mg and nicardipine infusion was 5 (1-14) mg/h. Initial BP was similar in the two groups. The nicardipine group had less BP variability (N 8.19 vs. L 10.78 mmHg; p = 0.003), fewer dosage adjustments [L 4 (1-17), N 2 (0-5); p < 0.001] and fewer additional antihypertensive agents (L 33%, N 8%; p = 0.013) administered during the 24-h observation period. In patients with ICH, 33% of nicardipine-treated patients achieved target BP within the first 60 min versus 6% of the L group (p = 0.02). Overall, incidence of hypotension (SBP < 90 mmHg) (L 3%; N 0%) and bradycardia (HR < 60 beats per min) (L 20.6%; N 12%) were comparable between the groups. CONCLUSIONS: Nicardipine offers an alternative to labetalol with similar tolerability and appears to provide a smoother blood pressure control compared to labetalol.

Effect of vasoactive therapy on cerebral circulation.

Many questions regarding blood pressure management after acute stroke remain unanswered, resulting in an ongoing debate about whether to treat hypertension acutely and how aggressively blood pressure should be lowered. This review discusses normal and altered cerebrophysiology and provides evidence supporting and opposing the active management of blood pressure within the first 24 hours after stroke. Commonly used intravenous antihypertensive agents and their cerebrovascular effects are reviewed, and therapeutic recommendations are given based on the available evidence.

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage: an overview of pharmacologic management.

Cerebral vasospasm remains one of the leading causes of mortality in patients who experience a subarachnoid hemorrhage but survive the initial 24 hours. Vasospasm generally occurs 3-4 days after the initial subarachnoid hemorrhage and peaks at 5-7 days. The pathophysiology of vasospasm is poorly understood, which directly contributes to the inconsistency of management and creates a formidable challenge in clinical practice. Traditionally, hemodilution, hypervolemia, and induced hypertension (so-called triple H therapy); calcium channel blockers; and endovascular therapy have been used as either prophylactic therapy or treatment. However, management of vasospasm varies among physicians and institutions mainly because of a lack of large clinical trials and inconsistent results. Practice has been based primarily on case reports and the preference of each practitioner. Several experimental therapies have been explored; however, large, prospective, randomized controlled trials are needed to elucidate the role of these therapies.