Delayed-Onset Malignant Hyperthermia in Association with Rocuronium Use

Purpose Two cases of malignant hyperthermia suspected to be related to the use of a nondepolarizing neuromuscular blocker are reported. Summary A pharmacogenetic disorder that may occur in as many as 1 in 3000 anesthesia procedures, malignant hyperthermia has been linked to the use of certain anesthetic gases and depolarizing neuromuscular blocking agents (e.g., succinylcholine). Although nondepolarizing neuromuscular blockers were cited as contributing to the development of malignant hyperthermia in a small number of published reports, the agents are generally considered safe for use in at-risk patients. Here investigators report two cases in which the nondepolarizing agent rocuronium is thought to have triggered malignant hyperthermia in patients with no known history of the disorder. In one case, a critically ill 27-year-old man undergoing an induced-hypothermia protocol developed a fever about 4 days after receiving rocuronium infusions, with temperatures rising over 11 days to a maximum of 105.2 °F. In the other case, a 63-year-old man being treated for serious complications of elective surgery developed extreme fever (maximum temperature of 107.1 °F) about 4 days after receiving two bolus doses and a continuous infusion of rocuronium. In both cases, the discontinuation of rocuronium therapy was followed by the rapid diminution of fever over 12–36 hours. After consultations with medical staff and consideration of other potential causal and contributory factors (e.g., neurologic injury, antimicrobial-induced fever), rocuronium was deemed the most likely trigger of the severe febrile response experienced by these two patients. Conclusion A 27-year-old man and a 63-year-old man received rocuronium and subsequently developed delayed-onset malignant hyperthermia, which resolved after the rocuronium was discontinued

Rocuronium and Malignant Hyperthermia

Authors response to a comment on: Beggs A, McCann J, Powers J. “Delayed-onset malignant hyperthermia in association with rocuronium use ” Am J Health-Syst Pharm 2012; 69:1128-34

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Predicting discharge to institutional long-term care following acute hospitalisation: a systematic review and meta-analysis

Background: moving into long-term institutional care is a significant life event for any individual. Predictors of institutional care admission from community-dwellers and people with dementia have been described, but those from the acute hospital setting have not been systematically reviewed. Our aim was to establish predictive factors for discharge to institutional care following acute hospitalisation. Methods: we registered and conducted a systematic review (PROSPERO: CRD42015023497). We searched MEDLINE; EMBASE and CINAHL Plus in September 2015. We included observational studies of patients admitted directly to long-term institutional care following acute hospitalisation where factors associated with institutionalisation were reported. Results: from 9,176 records, we included 23 studies (n = 354,985 participants). Studies were heterogeneous, with the proportions discharged to a care home 3–77% (median 15%). Eleven studies (n = 12,642), of moderate to low quality, were included in the quantitative synthesis. The need for institutional long-term care was associated with age (pooled odds ratio (OR) 1.02, 95% confidence intervals (CI): 1.00–1.04), female sex (pooled OR 1.41, 95% CI: 1.03–1.92), dementia (pooled OR 2.14, 95% CI: 1.24–3.70) and functional dependency (pooled OR 2.06, 95% CI: 1.58–2.69). Conclusions: discharge to long-term institutional care following acute hospitalisation is common, but current data do not allow prediction of who will make this transition. Potentially important predictors evaluated in community cohorts have not been examined in hospitalised cohorts. Understanding these predictors could help identify individuals at risk early in their admission, and support them in this transition or potentially intervene to reduce their risk

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Case Report - Apparent Epinephrine Toxicity in the Treatment of Anaphylaxis: A Patient Case of Prolonged Hypotension

Background: The emergent nature of anaphylaxis creates an environment of heightened risk for epinephrine medication misadventures that may occur in any health care setting. Literature to date has focused on the immediate adverse outcomes associated with epinephrine dosing and administration errors, with a lack of data available on prolonged consequences. Objective: We present a unique case of refractory hypotension associated with the administration of high-dose epinephrine for the treatment of anaphylaxis that prompted a comprehensive safety evaluation and implementation of a process improvement plan for all patients experiencing an anaphylactic reaction in our institution. Case Report: A 29-year-old female presented to an immediate care facility for treatment of anaphylaxis including 2 doses of epinephrine 1 mg (1:1000) intramuscularly. The patient was subsequently transported to our adult emergency department and developed isolated hypotension refractory to fluid resuscitation. The patient was then admitted to the medical intensive care unit with a diagnosis of epinephrine toxicity. The prolonged hypotensive response seen in this patient is believed to be a result of residual stimulation of the more sensitive beta receptors by high doses of epinephrine administered to the patient, resulting in a prolonged vasodilatory response. Conclusion: Epinephrine is a high-alert medication used for the treatment of anaphylaxis. Proactive evaluation of current processes among institutions is recommended in order to minimize dosing and administration errors with epinephrine as these errors can lead to substantial harm to patients

A Practical Approach to Hyperglycemia Management in the Intensive Care Unit: Evaluation of an Intensive Insulin Infusion Protocol

STUDY OBJECTIVES: To evaluate the effectiveness and safety of maintaining a target blood glucose concentration of 91-130 mg/dl with a standardized, nurse-managed, intensive insulin infusion protocol outside a study setting, and to determine if a statistically significant favorable effect on morbidity and mortality was achieved. DESIGN: Retrospective, observational, chart review. SETTING: Medical and surgical intensive care units (ICUs) in a community teaching hospital. PATIENTS: One hundred forty-three adult patients who received insulin infusions managed at the discretion of the physician over a 1-year period before initiation of the protocol (control group), and 70 patients who received insulin infusions over a 6-month period with infusion dosages titrated by using the protocol (protocol group). MEASUREMENTS AND MAIN RESULTS: Episodes of hypoglycemia, time within target range, mean blood glucose concentration, frequency of measurement, length of ICU stay, duration of mechanical ventilation, and overall mortality were collected. Hypoglycemic episodes were not significantly different between the groups. Blood glucose concentrations were within target range in 34% of all measurements in the protocol group compared with 23% in the control group (p\u3c0.001, relative risk [RR] 1.48, 95% confidence interval [CI] 1.38-1.58). Once target range was reached on one measurement, 43% of concentrations remained in target range in the protocol group compared with 29% in the control group (p\u3c0.001, RR 1.47, 95% CI 1.38-1.56). Frequency of measurements was higher in the protocol group versus control group (p=0.01); however, clinical difference was minimal. Protocol group had lower overall mortality rate (27% [19/70] vs 32% [46/143], p=0.45), reduced mean ICU length of stay (16.7 +/- 10.6 vs 18.4 +/- 16.0 days, p=0.37), and less mechanical ventilation time (16.5 +/- 9.7 vs 17.0 +/- 15.0 days, p=0.79). CONCLUSION: The nurse-managed insulin infusion protocol improved glycemic control with minimal hypoglycemic episodes compared with baseline practice. A trend toward decreased mortality, ICU length of stay, sand days of mechanical ventilation was observed. When compared with other published protocols, our insulin protocol displays comparable effectiveness with the use of less-frequent blood glucose measurements