Hours Of Discontinuation Research Articles

Evaluation of Dexmedetomidine Withdrawal and Management After Prolonged Infusion

Dexmedetomidine is often used for longer than its labeled indication of 24 hours, raising concerns for potential withdrawal. Data are limited regarding this syndrome in adult patients. This study aimed to further characterize dexmedetomidine withdrawal in critically ill adult patients after prolonged use. This was an institutional review board-approved, single-center, retrospective chart review conducted at a tertiary academic medical center. Adult intensive care unit (ICU) patients on dexmedetomidine for ≥72 hours in 2019 were screened for inclusion. Exclusion criteria were interruption of dexmedetomidine for >6 hours, indications for dexmedetomidine other than sedation, or patients with neurological or burn injury. The major end point was the incidence of dexmedetomidine withdrawal, defined as meeting ≥2 of the following criteria within 24 hours of discontinuation: newly positive Confusion Assessment Method for ICU, Richmond Agitation Sedation Scale score of ≥+2, hypertension, and tachycardia. Minor end points were incidence of individual withdrawal signs as previously described, additional sedatives or antipsychotics required, dose and duration of dexmedetomidine infusion, length of ventilation, ICU and hospital length of stay, and new onset of the following: fever, vomiting, loose stools/diarrhea, diaphoresis, or seizure. Of the 152 patients included, dexmedetomidine withdrawal occurred in 54 patients (35.5%). Rebound hypertension was the most common withdrawal sign (47 patients [87.0%]). In the withdrawal group, significantly more patients required additional β-blockers (29 [53.7%] vs 10 [10.2%]; P < 0.01), were reinitiated on dexmedetomidine (16 [29.6%] vs 10 [10.2%]; P < 0.01), and required a start or increased dose of clonidine (6 [11.1%] vs 3 [3.1%]; P = 0.04). There was no significant difference in the cumulative dose or duration of dexmedetomidine between the groups. Length of ventilation was longer in the withdrawal group (171 hours [83.7-280.8 hours] vs 159 hours [149.0-335.7 hours]; P < 0.01), but there was no difference in ICU or hospital length of stay. Prolonged use of dexmedetomidine was associated with withdrawal syndrome in 35.5% of patients in our study. Larger trials are needed to confirm the risk factors for dexmedetomidine withdrawal and identify measures to prevent withdrawal.

Effect of Phototherapy on Transcutaneous vs Total Serum Bilirubin Level in Preterm Neonates- A Prospective Cohort Study

Introduction: Neonatal jaundice is one of the most common problems encountered in the first week after birth. Neonates who develop significant hyperbilirubinemia require phototherapy. Delay in the diagnosis and management of jaundice may lead to neonatal morbidity and mortality. Total Serum Bilirubin (TSB) estimation is considered the gold standard method. However, this invasive procedure causes pain, anxiety, and may lead to infection and iatrogenic anaemia, especially in preterm neonates. Transcutaneous Bilirubin (TcB) estimation, which measures bilirubin through the skin, has been proposed as an alternative screening method for hyperbilirubinemia in term and near-term neonates. Aim: To compare TcB to TSB in preterm neonates of 30-34 6/7 weeks gestational age before, during, and after phototherapy. Materials and Methods: This hospital-based prospective cohort study was conducted at SDMCMS&amp;H, Dharwad, Karnataka, India, between December 2019 and November 2020. A total of 100 preterm neonates between 30 to 34 6/7 weeks of gestation with clinically suspected jaundice were enrolled in the study. TSB was measured in the laboratory using the Diazo Method, while TcB was measured using the Drager jaundice meter JM 103. TcB and TSB were measured and compared in preterm neonates with clinically suspected jaundice before phototherapy, during phototherapy (8 to 12 hours after initiation), and after 12- 18 hours of discontinuation of phototherapy. The collected data was analysed statistically using the mean, standard deviation, dependent t-test, Karl Pearson’s correlation coefficient, and scatter plots. Results: This study enrolled 100 neonates diagnosed with neonatal jaundice, of which 57 were males and 43 were females, resulting in a male-to-female ratio of 1:1.3. Phototherapy was administered to neonates with TSB values, with 79% of the babies between 30-32 weeks and 21% between 32-34 weeks. In the present study, TcB and TSB were compared before, during, and after phototherapy, and the results were analysed, showing statistical significance. The mean TcB levels were 12.05, 9.66, and 7.23 before, during, and after phototherapy, respectively. The mean TSB levels were 11.28, 10.16, and 7.65 before, during, and after phototherapy, respectively. Based on Karl Pearson’s correlation coefficient, a positive correlation was found between TcB and TSB before (r=0.8319, p-value &lt;0.001), during (r=0.6069, p &lt;0.001), and after phototherapy (r=0.8154, p&lt;0.001). Conclusion: TcB values are comparable to TSB values and can be adopted as the standard method to measure bilirubin levels in preterm babies in a clinical setting.

PMON01 Alpelisib (PI3-K Inhibitor) Induced Severe Insulin Resistance Complicated by Diabetic Ketoacidosis (DKA) with Rapid Reversal Following Discontinuation: A Case Report

Abstract Background Alpelisib is a phosphatidylinositol-3-kinase (PI3K) inhibitor, recently approved for treatment of metastatic breast cancer with PIK3CA mutation. The PI3K is involved in insulin signaling pathway and is responsible for translocation of GLUT-4 transporters in insulin responsive tissues and thus modulates insulin sensitivity. Impairment of PI3K pathway results in insulin resistance. Hyperglycemia is a known side effect of alpelisib, however there are only 5 reported cases of alpelisib induced DKA in literature. We describe a patient with Type 2 DM and metastatic breast cancer started on alpelisib with resultant rapid worsening of insulin resistance requiring substantially increased doses of insulin ultimately leading to DKA. She later had rapid reversal of insulin resistance with discontinuation of alpelisib. The degree and rapid onset/reversal of insulin resistance is highlighted in this case. Case 59-year-old female with Type-2 DM, metastatic breast cancer with PIK3CA mutation was started on alpelisib 300mg daily after inadequate response to other agents. Her insulin regimen prior to starting was degludec(U100) 35 units daily and humalog(U100) 30 units with meals. In the first week of starting alpelisib, her continuous glucose monitor(CGM) showed a dramatic increase in glucose values &amp;gt;400 mg/dL accompanied with polyuria and polydipsia. Anti-GAD and Islet-cell-antibodies were negative with C-peptide of 1.55 ng/mL with glucose of 378 mg/dL. Patient was hospitalized with DKA during month 4 of treatment after continuous up titration of her insulin therapy outpatient. With resolution of DKA, patients’ glucoses were well controlled when transitioned to a regimen of degludec 50 units and humalog 12 units with meals. Once alpelisib was restarted during this hospitalization, patient's glucoses increased from 140mg/dL to &amp;gt;400 mg/dL in just 4 hours after administration. Patient was ultimately discharged on a significantly higher dose insulin regimen of degludec 140 units daily and humalog 85 units TID as well as metformin and dulaglutide. A restaging scan demonstrated progression of her cancer and alpelisib was hence discontinued. We instructed the patient to decrease the dose of insulin from the day alpelisib is discontinued to degludec 10 units (.15 units/kg) and a correction scale with meals to assess new insulin requirements. Within the first 24 hours, patient's glucose improved significantly and remained well controlled with degludec 10 units daily and Humalog 5 units with meals. Conclusion The degree of alpelisib induced insulin resistance is often severe with significant increase in insulin requirements. The time to onset and reversal of alpelisib induced insulin resistance is often rapid and providers need to anticipate a rapid increase in insulin requirements within a few days of starting alpelisib and adjust doses promptly to prevent potential complication of DKA. Providers should also anticipate a rapid decrease in insulin requirements within 24 hours of discontinuation to prevent potential hypoglycemic events. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Factors Associated With Rebound Pain After Patient-controlled Epidural Analgesia in Patients Undergoing Major Abdominal Surgery: A Retrospective Study.

Although patient-controlled epidural analgesia (PCEA) is an effective form of regional analgesia for abdominal surgery, some patients experience significant rebound pain after the discontinuation of PCEA. However, risk factors for rebound pain associated with PCEA in major abdominal surgery remain unknown. This study evaluated the incidence of rebound pain related to PCEA and explored potential associated risk factors. We performed a retrospective review of 236 patients using PCEA following hepatobiliary and pancreas surgery between 2018 and 2020 in a tertiary hospital in South Korea. Rebound pain was defined as an increase from well-controlled pain (numeric rating scale <4) during epidural analgesia to severe pain (numeric rating scale ≥7) within 24 hours of discontinuation of PCEA. Logistic regression analysis was performed to determine the factors associated with rebound pain. Patients were categorized into the nonrebound pain group (170 patients; 72%) and the rebound pain group (66 patients; 28%). Multivariable logistic regression analysis revealed that preoperative prognostic nutritional index below 45 (odds ratio=2.080, 95% confidential interval=1.061-4.079, P =0.033) and intraoperative transfusion (odds ratio=4.190, 95% confidential interval=1.436-12.226, P =0.009) were independently associated with rebound pain after PCEA discontinuation. Rebound pain after PCEA occurred in ~30% of patients who underwent major abdominal surgery, resulting in insufficient postoperative pain management. Preoperative low prognostic nutritional index and intraoperative transfusion may be associated with rebound pain after PCEA discontinuation.

A Rare Case of ACE Inhibitor-Induced Intestinal Angioedema Presenting as a Delayed Complication in a Heart Transplant Recipient

<h3>Introduction</h3> ACE inhibitor-induced intestinal angioedema is a rare side effect of ACEi that presents with nonspecific signs and symptoms. Although the risk of occurrence is greater early in therapy, angioedema can present at any time and thus a high index of suspicion is needed to avoid delays in diagnosis, unnecessary testing, and considerable morbidity. <h3>Case Report</h3> Our patient is a 54-year-old male with past medical history of orthotopic heart transplantation 3 years prior for history of end-stage ischemic cardiomyopathy, heparin-induced thrombocytopenia, and hypertension who presented with 3 days of crampy abdominal pain rated 4 out of 10. He also had bloating and watery diarrhea. He had no fever, nausea or vomiting. The patient had rebound tenderness on physical examination. Labs were unremarkable. GI pathogen panel was negative including C. difficile. CT showed a moderate segment of distal ileum which demonstrated acute inflammatory changes including mucosal hyperemia and mural edema on a background of moderate ascites. GI were consulted and performed colonoscopy that revealed no significant abnormalities. The patient had been on lisinopril for 3 years to treat hypertension. This was subsequently stopped due to suspicion of intestinal angioedema. His symptoms resolved within 72 hours of discontinuation. <h3>Summary</h3> Isolated intestinal angioedema secondary to ACEi is a diagnosis of exclusion that necessitates awareness among physicians, particularly in vulnerable subgroups such as heart transplant patients. Symptoms classically subside within 24 to 48 hours after discontinuation of the ACEi.

Safety of Intravenous Cangrelor Administration for Antiplatelet Bridging in Hospitalized Patients: A Retrospective Study.

We aimed to characterize outcomes associated with cangrelor administration used in an antiplatelet bridging strategy in real-world clinical scenarios within a large academic medical system. Cangrelor has been used for antiplatelet bridging in perioperative settings or for patients unable to take oral medications. Prior studies in these settings have reported bleeding rates from 0%-40%. Patients were retrospectively identified via chart review and included if they were over 18 years old, had coronary or peripheral arterial stents, and had received at least 1 hour of cangrelor infusion during inpatient admission. The primary endpoint was Bleeding Academic Research Consortium (BARC) 3-5 bleeding during cangrelor infusion or within 48 hours of discontinuation; secondary endpoints were bleeding events defined by Thrombolysis in Myocardial Infarction (TIMI), Global Use of Strategies to Open Occluded Arteries (GUSTO), and International Society on Thrombosis and Hemostasis (ISTH) criteria, as well as BARC 2 bleeding. Thirty-one patients met the inclusion criteria. Cangrelor indications were bridging to procedure in 22 patients (71.0%) and inability to take oral P2Y12 inhibitors in 9 patients (29.0%). Twenty-three patients (74.2%) were men, 11 patients (35.5%) were in cardiogenic shock, and 4 patients (12.9%) were on extracorporeal membrane oxygenation (ECMO) at the time of administration. No patients received cangrelor for routine percutaneous coronary intervention. Of the 31 patients, 13 (41.9%) had BARC 3-5 bleeding and 7 (22.6%) expired during hospitalization. All 4 patients on ECMO suffered BARC 3-5 bleeding. We reviewed the use of cangrelor for antiplatelet bridging in real-world clinical scenarios and observed higher rates of clinically significant bleeding than seen in other similar studies. Our study suggests careful consideration when using cangrelor in a sick patient population.

DOXYCYCLINE INTAKE AND DISTRIBUTION IN THE BODY OF BROILER CHICKENS WITH ORNITHOBACTERIOSIS

The clinical efficiency of the antibiotic is determined by its distribution in organs and tissues, the ability to penetrate the physiological and pathological barriers of the body. The article presents the results from a study of the intake, distribution, and excretion of doxycycline hyclate – the active substance of the antibiotic pollodoxin from the body of broiler chickens (the Cobb-500 cross) with ornithobacteriosis. It has been established that 24 hours after the pollodoxin solution application in broiler chickens with ornithobacteriosis, the highest content of its active substance (doxycycline hyclate) was found in the lungs, liver, slightly less – in the kidneys, and least – in the heart and pectoral muscles. After 48 and 72 hours, the content of doxycycline hyclate increases in the liver, kidneys, heart, and pectoral muscles compared to 24 hours, while in the lungs decreases slightly after 48 hours and does not differ from it after 72 hours. At 96 hours, the content of doxycycline hyclate in the kidneys, lungs, and pectoral muscles reaches maximum values; in the liver it is smaller than the previous one (72 hours), while in the heart it does not differ from it. Doxycycline hyclate does not show cumulative properties and “organ affiliation” during 96 hours of entry into the body of broiler chickens with ornithobacteriosis. After 24 hours of discontinuation of pollodoxin use (120 hours of the experiment), the content of doxycycline hyclate in all studied organs decreases but remains high enough, indicating a relatively long elimination half-life and antimicrobial action. Pharmacokinetic indicators will allow the doctor to determine an effective drug that will provide a therapeutic effect and will prevent the development of resistance of microorganisms. Keywords: pollodoxin, doxycycline hyclate, broiler chickens, ornithobacteriosis, Ornithobacterium rhinotracheale, pharmacokinetic parameters

Heroin-induced headache in female heroin addicts

ObjectiveTo investigate the manifestations and incidence of headaches caused by heroin in Chinese women.MethodsThis was a survey study conducted from 29 June to 3 July 2015 with women attending the Shanxi Drug Rehabilitation Centre for Women (China). All study subjects were newly admitted and had not begun their drug rehabilitation. Demographic characteristics, heroin usage and headache episodes within the previous 3 months were surveyed, especially the presence of a headache within 2 hours of heroin use. Details of the severity, location, premonitory symptoms and characteristics of headaches were recorded.ResultsOf the 90 heroin-dependent patients, 74 experienced headache attacks within 2 hours of heroin use, and the headaches subsided within 72 hours of discontinuation of heroin use. Most heroin-induced headaches were similar to migraines and manifested as pulsating pain in 54 patients (51/74, 68.9%); bilateral pain was reported by 46 patients (46/74, 62.2%). Approximately half of the patients with heroin-induced headaches also reported accompanying symptoms of nausea, vomiting, and light and sound sensitivity.ConclusionsHeroin-induced headache may eventually be listed as a new class of headache in the International Classification of Headache Disorders.

Impact of Pharmacist-Directed Simplified Procalcitonin Algorithm on Antibiotic Therapy in Critically Ill Patients With Sepsis.

The purpose was to determine whether a simplified procalcitonin (PCT) algorithm guided by pharmacist recommendations reduces antibiotic duration of therapy in critically ill patients with suspected sepsis. This was a single-centered pre-post study conducted at a 1368-bed community teaching hospital in the United States. A prospective cohort with pharmacist intervention utilizing a simplified PCT algorithm was compared with a retrospective historical cohort with standard therapy. Adult patients admitted to the intensive care unit (ICU) with suspected sepsis who received intravenous antibiotics were included. A pharmacist recommended continuation or discontinuation of antibiotics based on the PCT level per our algorithm and full clinical assessment of the patient. Primary outcome was total duration of antibiotic therapy. Secondary outcomes were ICU and hospital length of stay (LOS), reinitiation of antibiotic therapy within 72 hours of discontinuation, and 28-day in-hospital mortality. From September 2017 to May 2018, 360 patients were screened for eligibility. Of these, 26 patients were included in the PCT group and 26 patients in the standard therapy group. Baseline characteristics were similar between groups. A significant difference in duration of antibiotic therapy was detected with a median of 9 days in the PCT group versus 12 days in the standard therapy group (P = .02). There were no significant differences in secondary endpoints of ICU and hospital LOS, reinitiation of antibiotics at 72 hours, or 28-day mortality. Use of a simplified PCT algorithm with pharmacist-guided recommendations significantly reduced the duration of antibiotic therapy in critically ill patients with sepsis.

The effect of heparin infusion intensity on outcomes for bridging hospitalized patients with atrial fibrillation.

BackgroundPerioperative bridging in atrial fibrillation (AF) is associated with low thromboembolic rates but high bleeding rates. Recent guidance cautions the practice of bridging except in high risk patients. However, the practice of bridging varies widely and little data exist regarding appropriate anticoagulation intensity when using intravenous unfractionated heparin (UFH).HypothesisTo determine if high intensity UFH infusion regimens are associated with increased bleeding rates compared to low intensity regimens for bridging patients with AF.MethodsWe conducted a single center retrospective cohort study of admitted patients with non‐valvular AF receiving UFH for ≥24 hours. UFH intensities were chosen at the providers' discretion. The primary endpoint was the rate of bleeding defined by the International Society on Thrombosis and Hemostasis during UFH infusion or within 24 hours of discontinuation. The secondary endpoint was a composite of cardiovascular events, arterial thromboembolism, venous thromboembolism, myocardial infarctions and death during UFH infusion.ResultsA total of 497 patients were included in this analysis. Warfarin was used in 82.1% and direct acting oral anticoagulants in 14.1% of patients. The rate of any bleed was higher among high intensity compared to low intensity UFH regimens (10.5% vs 4.9%, odds ratio = 2.29, 95% confidence interval = 1.07‐4.90). Major bleeding was significantly higher among high intensity compared to low intensity UFH regimens. There was no difference in composite thrombotic events or death.ConclusionsLow intensity UFH infusions, targeting lower anticoagulation targets, were associated with decreased bleeding rates without a signal of increased thromboembolic events in hospitalized AF patients.

Impact of the Sequence of Norepinephrine and Vasopressin Discontinuation in Patients Recovering From Septic Shock.

Background: Septic shock is a serious medical condition affecting millions of people each year and guidelines direct vasopressor use in these patients. However, there is little information as to which vasopressor should be discontinued first. Objective: The objective of this study was to assess the impact of the sequence of norepinephrine and vasopressin discontinuation on intensive care unit (ICU) length of stay. Methods: This was a single-center retrospective cohort study conducted at The University of Tennessee Medical Center in Knoxville, Tennessee. Patients included in this study were adults 18 years of age and older with a diagnosis of septic shock who received norepinephrine in combination with vasopressin. Patients were excluded if norepinephrine or vasopressin were not the last 2 vasoactive agents used or if the patient expired or care was withdrawn. Measurements and Main Results: A total of 86 patients were included in this study, with 34 patients in the norepinephrine discontinued first group (NDF) and 52 in the vasopressin discontinued first group (VDF). For the primary outcome of ICU length of stay, no statistically significant difference was found between the NDF and the VDF groups (9.38 days vs 11.07 days, P = .313). The secondary outcome of the dose of norepinephrine at which vasopressin was initiated was also found to not be significant between the NDF and VDF groups (22 µg/min vs 31.1 µg/min, P = .11). The rates of hypotension within 24 hours of discontinuation of the first agent were also not significant between the NDF and VDF groups (17% vs 31%, P = .38). Conclusions: Based on the results of this study, there was significant no difference in ICU length of stay based on the sequence of discontinuation between norepinephrine and vasopressin in patients recovering from septic shock.

72 Offset of ticagrelor prior to coronary artery bypass graft surgery (cabg) surgery

IntroductionTicagrelor is a more potent platelet inhibitor than clopidogrel but also has a more rapid offset of inhibitory effect. The optimal timing of discontinuation of ticagrelor prior to coronary artery...

Alprazolam withdrawal delirium and brief reversible psychosis: a case report.

To the Editor: Documented cases of sedative, hypnotic, or anxiolytic withdrawal delirium are highlighted by autonomic instability, as well as particular physical examination findings that characterize the suspected diagnosis. We present a patient with alprazolam withdrawal delirium, who lacks measurable signs of withdrawal, including but not limited to, significant examination findings of tremor, psychomotor agitation, or grand mal seizures. Case report: Mr A, a 33-year-old Middle Eastern man, was brought to the emergency department in 2014 for the investigation of altered mental status following alprazolam withdrawal 2 days prior. Previously, he had been prescribed alprazolam 4 mg daily. Subsequent to completion of his prescription, Mr A exhibited expansive behavior and hypervigilance, with periods of collapsing to appear dead. He also had recurrent delusions involving harm to both family and self. Mr A reportedly admitted to abusing alprazolam, consuming 6–7 pills (total 14 mg) daily. Based on the recommendation of Mr A’s primary care physician, the family administered an extra dose of risperidone 2 mg, trazadone 100 mg, and buspirone 15 mg to help calm him, which was unsuccessful. He received alprazolam 2 mg in route to the hospital. After presenting to the emergency department, Mr A displayed altered consciousness; disorientation to person, time, and purpose; flight of ideas; poor judgment and insight; and bizarre, agitated, and delusional behavior but no suicidal ideation. He received regularly scheduled doses of medications in the emergency department. Mr A’s vital signs were within normal limits; his physical examination was unremarkable. Results of extensive laboratory work, including electrolytes, renal and liver function tests, and complete blood counts, were within normal limits. The urine toxicology screen was negative for amphetamines, cannabis, hallucinogens, benzodiazepines, cocaine, opiates, and 3,4-methylenedioxymethamphetamine. His blood alcohol result was < 0.01%. Workup for sudden onset of altered mental status revealed no abnormal results. Initial psychiatric evaluation obtained in the emergency department revealed disorientation to person, time, and purpose; poor judgment and insight; poor concentration; poor recent and remote memory; and no suicidal or homicidal ideation. Mr A was placed on involuntary commitment and transferred to a psychiatric hospital for further management. A diagnosis of alprazolam withdrawal delirium and brief reversible psychosis (DSM-5 criteria for sedative, hypnotic, or anxiolytic withdrawal) was made. Mr A denied any psychiatric history and was physically healthy. Family expressed that he had a history of suicidal ideation, homicidal ideation, and violence toward others. Other pertinent details relayed by family included a history of anxiety, depression, and previous inpatient psychiatric admissions. Prior to admission to the emergency department, Mr A’s father, the primary caregiver, stated that he noticed the alprazolam pill counts were inaccurate. Soon after, his son’s behavior became bizarre; specifically, Mr A demonstrated prolonged periods of wakefulness and verbalized threats to harm himself and his family. Diagnostic features of sedative, hypnotic, or anxiolytic withdrawal are highlighted by 2 or more symptoms including “autonomic hyperactivity (eg, increases in heart rate, respiratory rate, blood pressure, or body temperature, along with sweating); a tremor of the hands; insomnia; nausea, sometimes accompanied by vomiting; anxiety; and psychomotor agitation. 1(p558) We present a case of reversible brief delirium and psychotic episode following withdrawal of alprazolam in an otherwise healthy young man. Our case shows that sedative, hypnotic, or anxiolytic withdrawal delirium can occur in the absence of cardinal withdrawal symptoms. Alprazolam withdrawal delirium and brief psychosis is reversible and can be treated with use of long-acting benzodiazepines. In our case, we used clonazepam to control symptoms of alprazolam withdrawal delirium and psychosis. According to PubMed, there are 3 published cases of alprazolam withdrawal delirium4–6; all 3 patients experienced autonomic instability in the presence of delirium and brief reversible psychosis. In conclusion, physicians should be aware of the possibility of alprazolam withdrawal delirium and brief reversible psychosis in the absence of cardinal withdrawal symptoms as outlined in the DSM-5. Alprazolam withdrawal should be included in the differential diagnosis of conditions with sudden onset of delirium and brief psychotic symptoms in younger individuals experimenting with illicit substances despite a negative toxicology screen. An increased incidence of reversible brief psychotic episodes might be induced by the short-acting benzodiazepine alprazolam, which is undetected in routine urine or blood drug screen after only 24 hours of discontinuation.

High-dose midazolam infusion for refractory status epilepticus

This study compares 2 treatment protocols allowing low vs high continuous IV midazolam (cIV-MDZ) doses. We compared adults with refractory status epilepticus treated with a protocol allowing for high-dose cIV-MDZ (n = 100; 2002-2011) with those treated with the previous lower-dose cIV-MDZ (n = 29; 1996-2000). We collected data on baseline characteristics, cIV-MDZ doses, seizure control, hospital course, and outcome. Median maximum cIV-MDZ dose was 0.4 mg/kg/h (interquartile range [IQR] 0.2, 1.0) for the high-dose group and 0.2 mg/kg/h (IQR 0.1, 0.3) for the low-dose group (p < 0.001) with similar duration of infusion. Median time from status epilepticus onset to cIV-MDZ start was 1 day (IQR 1, 3) for the high-dose group and 2 days (IQR 1, 5) for the low-dose group (p = 0.016). "Withdrawal seizures" (occurring within 48 hours of discontinuation of cIV-MDZ) were less frequent in the high-dose group (15% vs 64%, odds ratio 0.10, 95% confidence interval 0.03-0.27). "Ultimate cIV-MDZ failure" (patients requiring change to a different cIV antiepileptic medication) and hospital complications were not different between groups. Hypotension was more frequent with higher cIV-MDZ doses but was not associated with worse outcome. Discharge mortality was lower in the high-dose group (40% vs 62%, odds ratio 0.34, 95% confidence interval 0.13-0.92 in multivariate analysis). High-dose cIV-MDZ treatment of refractory status epilepticus can be performed safely, is associated with a lower seizure rate after cIV-MDZ discontinuation, and may be associated with lower mortality than traditional lower-dose protocols. This study provides Class III evidence that midazolam at higher infusion rates is associated with a reduction in seizure recurrence within 48 hours after discontinuation and may be associated with lower mortality.

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Introduction: Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) is a rescue modality in refractory circulatory failure or severe respiratory failure, with a mortality rate of approximately 50%. However, little evidence exists regarding in-hospital mortality after discontinuing VA-ECMO. Hypothesis: The present study was conducted to investigate for in-hospital mortality of patients after discontinuing VA-ECMO. Methods: Between October 2008 and June 2012, patients undergoing VA-ECMO due to refractory postcardiotomy shock, cardiogenic shock and/or pulmonary dysfunction were screened, and those successfully weaned from VA-ECMO were included. Patients <18yo, or subsequently placed on a left ventricular assist device and/or undergoing transplantation were excluded. Results: Of 84 patients who underwent VA-ECMO, 50 patients were successfully weaned. There were 21(42%) surgical and 29 (58%) medical patients. The average age (± SD) was 65 ± 11yr, 80% were male, median hospital stay was 32.5d (range 19-61), and mean APACHE II score was 28.6 ± 7.2. After discontinuing VA-ECMO, 34 patients survived and 16 died. The median duration from discontinuing VA-ECMO to death was 9.5d (range 4.5-14.8). Causes of mortality included sepsis in 5 (31%), hepatic failure in 3 (19%), low cardiac output syndrome in 2 (13%), respiratory failure in 1 (6%), and other in 5 (31%). Two patients died within 48 hours of discontinuation. In multiple logistic regression analyses, continuous renal replacement therapy (CRRT) during VA-ECMO (OR: 45.9, 95%, CI 3.0 – 699.7) was significantly associated with increased in-hospital mortality. Conclusions: In-hospital mortality after discontinuing VA-ECMO is 32%, which is similar to previous study (J Thorac Cardiovasc Surg. 2001; 122: 92-102). This study shows that CRRT is a significant predictor of in-hospital mortality after discontinuing VA-ECMO and the main cause of death is sepsis.

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Introduction: Critically ill children in the pediatric intensive care unit (PICU) often receive multiple classes of sedatives and analgesics for comfort and safety. Dexmedetomidine is frequently added when a child proves challenging to sedate with traditional opioid and benzodiazepine regimens. Discontinuation of prolonged infusions of high dose dexmedetomidine may result in a clinical withdrawal syndrome similar to opioid withdrawal, and clonidine is utilized to treat children experiencing withdrawal. Hypothesis: We hypothesize that longer duration and higher dose of dexmedetomidine is associated with clinical withdrawal syndrome and discharge home on transdermal or oral clonidine. Methods: We performed a retrospective chart review from June 2011 to June 2012 of all children who received dexmedetomidine for sedation in the pediatric intensive care unit. Dosing variables for dexmedetomidine, concurrent administration of other sedatives, and documentation of withdrawal with the Withdrawal Assessment Tool (WAT-1) were collected. Results: 37 children received dexmedetomidine during the 12-month period studied. The average daily dose of dexmedetomidine was 1.1 mcg/kg/hour and the mean duration of administration was 12.2 days. 10 children (27%) were discharged home on clonidine. The presence of greater than two concurrent sedatives at the time of dexmedetomidine initiation was predictive of longer dexmedetomidine duration and higher average daily dose. Longer duration of dexmedetomidine was associated with increased WAT scores within 24 hours of discontinuation and higher doses of clonidine upon discharge to home. After adjustment for age, sex and duration of intubation, dexmedetomidine dose and duration were not associated with survival to discharge. Conclusions: These data support the role of dexmedetomidine as a cause of physiologic withdrawal in critically ill children receiving sedatives. As dexmedetomidine use becomes more widespread in the critically ill pediatric population, further research is necessary to determine the physiologic effects of discontinuation of this drug after prolonged duration of therapy, and long-term outcomes in children discharged home on clonidine.

Emotional lability secondary to the application of a very potent topical corticosteroid

A 66 yrs old gentleman presented with severe mood changes following application of very potent topical corticosteroid cream, clobetasol propionate, which was prescribed for his recalcitrant eczema. The symptoms disappeared within 24 hours of discontinuation of the cream and he remained mentally well when reviewed after 2 weeks.

Expanding the Use of Retinoids in Acute Myeloid Leukemia: Spotlight on Bexarotene

In this issue, Tsai et al. ([1][1]) report on a phase-I clinical trial of bexarotene in 27 non-M3 acute myeloid leukemia (AML). AML is characterized by abnormalities in the myeloid line at various stages of commitment and maturation, leading to an accumulation of granulocyte or monocyte precursors.

Aripiprazole-Associated Acute Dystonia

Back to table of contents Previous article Next article LETTERFull AccessAripiprazole-Associated Acute DystoniaMukesh Sanghadia M.D., M.R.C.Psych.,Narsimha Reddy Pinninti M.D.,Mukesh Sanghadia M.D., M.R.C.Psych.Search for more papers by this author,Narsimha Reddy Pinninti M.D.Search for more papers by this author,Published Online:1 Jan 2007AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: Aripiprazole is the latest addition to the armamentarium of antipsychotic agents available in the United States. It has been heralded as a third generation antipsychotic agent owing to its dual action as a dopamine autoreceptor agonist as well as the more conventional postsynaptic D 2 antagonist. 1 This is the first report, to our knowledge, of acute dystonia associated with aripiprazole in an adult, although it has been described in a young adult before. 2Case Report“Ms. W,” a 19-year-old Caucasian woman with normal developmental milestones, considered bright by her parents, presented with a history of obsessive concerns about getting “sick,” “poisoned,” and “contaminated” which had started at about age 9. Her school performance progressively declined to the degree that she barely graduated from high school, despite home schooling. Her parents described lack of ambition, volition, and sociality, with an indifferent attitude towards their concern over her functioning—a change from her previous personality. Substance and organic history was negative. The patient had been treated with fluoxetine and therapy before, and was taking sertraline, 200mg/day, and clonazepam, 0.25mg b.i.d., at presentation, with no benefit. A diagnosis of schizophrenia, undifferentiated type, was made, and the patient was started on a regimen of aripiprazole, 15mg/day. Sertraline and clonazepam were continued with the intent that these would be tapered off after aripiprazole was started. After the third day of taking aripiprazole, the patient complained (by e-mail), “My neck wants to stay sideways all the time.” She also complained of her lower jaw protruding to her right, the same side as her neck was turning to. There was no oculogyria or tongue dystonia. Ms. W stopped taking aripiprazole on her own and later reported that her side effects disappeared within 24 hours of discontinuation. There was no previous history of any movement disorder. She demonstrated the abnormal movements, consistent with acute dystonia, during a subsequent office visit. Acute dystonia with atypical antipsychotic agents, although relatively rare, has been reported with other atypical agents, including with clozapine. Their 5-HT 2A antagonism, as a group, likely explains their low potential for extrapyramidal side effects. 3 A likely explanation for acute dystonia in this case could be an increased plasma aripiprazole level due to inhibition of cytochrome P4502D6 by sertraline, for which both are substrates. 4 Further, there is a generally decreased clearance of aripiprazole in women. 4 Since aripiprazole levels were not obtained, this hypothesis remains untested. Caution when using aripiprazole with sertraline or another P450D26 inhibitor, especially in women, would seem appropriate. Borgess Medical Center, Kalamazoo, Mich.University of Medicine and Dentistry, New Jersey, School of Osteopathic Medicine, Cherry Hill, N.J.

Suspected β-Antagonist—Induced Thrombocytopenia

To report a case of possible beta-antagonist-induced thrombocytopenia. A 44-year-old African American woman with systemic lupus erythematosus developed thrombocytopenia. Splenic sequestration was suspected, but the rise in platelets after splenectomy was temporary. Bacterial and viral etiologies were ruled out, since thrombocytopenia continued 6 months after splenectomy. Her medications acetaminophen, amitriptyline, amlodipine, beta-antagonists, and diphenhydramine were suspected. Nadolol and labetalol were started immediately prior to splenectomy. Six months after splenectomy, the woman was hospitalized for pneumonia; the platelet count was 50 x 10(3)/mm(3). Nadolol was discontinued on day 2. Within 24 hours, the platelet count rose to 128 x 10(3)/mm(3) and exceeded 200 x 10(3)/mm(3) by day 7. Labetalol was discontinued on day 8, but no additional significant rise occurred. The patient developed thrombocytopenia one year later when placed on nadolol and famotidine during admission for a gastrointestinal bleed. The platelet count decreased during the admission. Both drugs were discontinued after the last platelet count (100 x 10(3)/mm(3)). The platelet count had normalized by the follow-up visit 16 days later and remained normal until the patient's death almost a year later. Thrombocytopenia is not a common adverse effect of beta-antagonist therapy. As of February 1, 2005, only 4 case reports of suspected beta-antagonist-associated thrombocytopenia have been published in English, and the medications cited are unavailable within the US. After splenectomy, the thrombocytopenia might have resolved if the beta-antagonists had not been present. Since thrombocytopenia resolved within 24 hours of discontinuation of nadolol, it is likely that the continued thrombocytopenia was beta-antagonist induced. The likelihood that the beta-antagonist caused the adverse event is possible according to the Naranjo probability scale. The temporal association between the discontinuation of nadolol and the rise in platelets suggests that the thrombocytopenia resulted from nadolol.