Atorvastatin versus Placebo in ICU Patients with COVID-19: Ninety-day Results of the INSPIRATION-S Trial.

BACKGROUND: In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days. METHODS: This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale. RESULTS: In the primary analysis, 587 patients were included (age: 57 [Q1-Q3: 45-68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60-1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42-0.86, p interaction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41-1.01, p = 0.05). CONCLUSION: Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508).

Sub dissociative dose of ketamine with haloperidol versus fentanyl on pain reduction in patients with acute pain in the emergency department; a randomized clinical trial.

BACKGROUND: Ketamine is known to be an effective factor in reducing pain without significant side effects. OBJECTIVE: One of the limited side effects of Ketamine is agitation. Due to the reduction of this symptom with Haloperidol, we decided to design a randomized clinical trial to compare the analgesic effect of Ketamine with Haloperidol and Fentanyl in reducing acute pain and its complications. METHODS: In this study, 200 adult patients who presented to the emergency department with acute pain are examined. They are randomly divided into two groups. One group received intravenous Ketamine with Haloperidol and the other group received intravenous Fentanyl. Patients are then compared for their pain score before and after administration of the drugs, as well as the side effects they experienced. RESULTS: There was no significant difference between the mean scores of initial pain in the two groups, but at all intervals of 5, 10, 15 and 30 min after injection, the mean of pain scores of patients in the group receiving Ketamine and Haloperidol were lower. The need for injection of rescue analgesic was 9% in the Ketamine and Haloperidol group and 34% in the Fentanyl group. The mean agitation score did not differ between the two groups except in the tenth minute. At tenth minute, the mean agitation score of the Ketamine group was higher. CONCLUSION: Ketamine works better than fentanyl in controlling acute pain, and limited side effect of agitation can be controlled if injected with haloperidol. Due to its better function and fewer side effects, it seems that in controlling acute pain, Ketamine along with Haloperidol can be a good alternative to opioids.

Intermediate-Dose versus Standard-Dose Prophylactic Anticoagulation in Patients with COVID-19 Admitted to the Intensive Care Unit: 90-Day Results from the INSPIRATION Randomized Trial.

BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. METHODS: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. RESULTS: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.

Predictive Utility of the Glasgow Coma Scale and the Head Abbreviated Injury Scale in Traumatic Brain Injury: Results from the National Trauma Registry of Iran.

BACKGROUND: Trauma severity indices are commonly used to describe the severity of sustained injuries in a quantitative manner perceivable by healthcare providers in different settings. In this study, we aimed to assess the predictive utility of the Glasgow Coma Scale (GCS) and the 2015 revision of the head Abbreviated Injury Scale (head AIS) as two of the most widely used severity indices for traumatic brain injury (TBI). METHODS: In this cross-sectional study, we used data from the National Trauma Registry of Iran. The area under the receiver operating characteristic curve (AUROC) was calculated to assess the utility of GCS and head AIS scores in predicting patients' outcomes. RESULTS: A total of 321 patients, predominantly males (81.9%) with an average age of 41.9 (±19.5) years were enrolled in the study. The most common cause of injury was road traffic accidents (73.5%) followed by falls (20.2%). The mean admission GCS and head AIS scores were 13.5 (±3.2) and 2.5 (±1.0), respectively. AUROC of the GCS was significantly higher than the head AIS for all outcome variables (P<0.05). AUROC of both severity scoring systems for predicting in-hospital mortality was significantly higher in the 15-44 age group than the 65 or older age group (P<0.05). CONCLUSION: Based on our study results, GCS had better performance in predicting patients' outcomes than the head AIS. Also, we found that age significantly affected the ability of these indices in predicting in-hospital mortality of TBI patients.

The influence of shift work on the psychomotor capabilities of emergency medicine residents.

OBJECTIVE: Shift work affects health status of healthcare providers and patients. We assessed the effect of shift work on psychomotor activities of emergency medicine residents of 3 university hospitals. METHODS: The participants were enrolled to perform selected psychomotor tests via the Vienna test system (VTS) after written consent. They passed 4 episodes of test performance before and after 2 consecutive day and night clinical shifts of 12 hours. The status of general health, circadian rhythm, sleepiness, smoking habits, and the scores of the cognition test (COG), the determination test (DT), and the visual pursuit test of emergency medicine residents were compared before and after morning and night shifts. RESULTS: Overall, 23 residents (34.8% were male) performed tests. The mean (SD) age was 35.7 + 8.5 years. The mean general health and circadian scores before and after day/night shifts were not different. The Stanford sleepiness scale showed higher scores after night shifts. In the cognition test, the sum of correct rejections was higher after day shifts. Moreover, in the DT results, correct responses were more prevalent, the omitted responses were fewer accompanied by better median reaction time after day shifts. The sum of correct rejections of the COG test showed difference in terms of improved results in night tests compared to day-shift tests. The mean reaction time of the DT showed significant difference with shorter reaction time in night-shift tests. The visual pursuit test results were not different between day and night shifts. CONCLUSIONS: Sleepiness was higher after night shifts. The results of selected psychomotor tests showed that the psychomotor function of the residents was not delayed or worse after night shifts in comparison to the day shifts.

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial.

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.

Comparing Diazepam Plus Fentanyl With Midazolam Plus Fentanyl in the Moderate Procedural Sedation of Anterior Shoulder Dislocations: A Randomized Clinical Trial.

BACKGROUND: The reduction of shoulder dislocation requires adequate procedural sedation and analgesia. The mixture of midazolam and fentanyl is reported in the literature, but long-acting benzodiazepines in conjunction with fentanyl are lacking. STUDY OBJECTIVE: Our aim was to compar e IV diazepam with IV midazolam in moderate procedural sedation (based on the classification of the American Society of Anesthesiologists) for the reduction of shoulder dislocation. METHODS: This was a randomized controlled clinical trial conducted from April 2019 to December 2019 in the emergency department of a university-affiliated hospital in Tehran, Iran. Participants were adult patients (aged 18-65 years) with anterior shoulder dislocation. Group A (n = 42) received diazepam 0.1 mg/kg plus fentanyl 1 µg/kg IV and group B received midazolam 0.1 mg/kg plus fentanyl 1 µg g/kg IV. Main outcomes measured were onset of muscle relaxation, time taken to reduction, total procedure time, number of the reduction attempts, patient recovery time, the occurrence of the adverse effects, amount of the pain reported by the patients using visual analog scale, and patients and physicians overall satisfaction with the procedure using a Likert scale question. RESULTS: Eighty-one patients were included. The mean ± standard deviation time of the onset of the muscle relaxation and time taken to reduction was shorter in the diazepam plus fentanyl group (p = 0.016 and p = 0.001, respectively). Adverse effects and pain relief were not statistically different between the two groups. Patient recovery time and total procedure time was shorter in the midazolam plus fentanyl group (p = 0.008 and p = 0.02, respectively). The overall satisfaction of patients and physicians was higher in the diazepam plus fentanyl group. CONCLUSIONS: As compared with midazolam plus fentanyl, diazepam plus fentanyl was superior in terms of the onset of the muscle relaxation, patient and physician satisfaction, and time taken to reduction.

National Guidelines for Cognitive Assessment and Rehabilitation of Iranian Traumatic Brain Injury Patients.

BACKGROUND: Individuals with moderate to severe traumatic brain injury (TBI) often have prolonged cognitive impairments, resulting in long-term problems with their real-life activities. Given the urgent need for evidence-based recommendations for neuropsychological management of Iranian TBI patients, the current work aimed to adapt eligible international guidelines for cognitive assessment and rehabilitation of the TBI patients in Iran. METHODS: The project was led by an executive committee, under the supervision of the Iranian Ministry of Health and Medical Education (MOHME). Following a systematic literature search and selection process, four guidelines were included for adaptation. Clinical recommendations of the source guidelines were tabulated as possible clinical scenarios for 90 PICO clinical questions covering all relevant phases of care. After summing up the scenarios, our initial list of recommendations was drafted according to the Iranian patients' conditions. The final decision-making, with the contribution of a national interdisciplinary panel of 37 experts from across the country, was conducted in two rounds using online and offline survey forms (Round 1), and face-to-face and telephone meetings (Round 2). RESULTS: A total of 63 recommendations in six sections were included in the final list of recommendations, among which 24 were considered as key recommendations. In addition, some of the recommendations were identified as fundamental, meaning that proper implementation of the other recommendations is largely dependent on their implementation. CONCLUSION: Iranian health policy makers and rehabilitation program managers are recommended to address some fundamental issues to provide the necessary infrastructure to set up an efficient cognitive rehabilitation service system.

Effects of Angiotensin Receptor Blockers (ARBs) on In-Hospital Outcomes of Patients With Hypertension and Confirmed or Clinically Suspected COVID-19.

BACKGROUND: There is an ongoing controversy about harms and benefits of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in hypertensive patients with coronavirus disease 2019 (COVID-19). Given the unresolved debate, we investigated the association of ARBs with in-hospital outcomes of these patients. METHODS: In this retrospective observational study, we studied patients with COVID-19 who referred to Sina Hospital in Tehran, Iran, from 20 February to 29 May 2020. Patients with either positive real-time reverse-transcriptase polymerase-chain-reaction test of swab specimens, or high clinical suspicion according to the World Health Organization's interim guidance were included. We followed-up patients for incurring death, severe COVID-19, and in-hospital complications. RESULTS: We evaluated 681 patients with COVID-19 of whom 37 patients were excluded due to incomplete medical records and 8 patients who used ACEIs which left 636 patients in the analysis. In this cohort, 108 (17.0%) patients expired and 407 (64.0%) patients incurred severe COVID-19. Of 254 (39.9%) patients with hypertension, 122 (48.0%) patients were receiving an ARB. After adjustment for possible confounders, we found no independent association between taking ARBs and in-hospital outcomes except for acute kidney injury (AKI), in patients with confirmed or clinically suspected COVID-19, either hypertensive or not-hypertensive. We found that discontinuation of ARBs during hospitalization was associated with a greater risk of mortality, invasive ventilation, and AKI (all P ˂ 0.002). CONCLUSIONS: We found that taking ARBs by patients with hypertension and confirmed or clinically suspected COVID-19 is not associated with poorer in-hospital outcomes after adjustment for possible confounders.

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies.

BACKGROUND: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. METHODS: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count <20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes >3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. CONCLUSIONS: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.

The assessment of ice pack effect in pain reduction during digital nerve block: A randomized clinical study.

OBJECTIVES: Digital nerve block is a painful procedure. Several methods have been proposed to decrease the injection pain. Applying an ice pack is a pertinent choice due to its effectiveness on pain reduction, convenience, and low costs. In this study, the degree of injection pain reduction was assessed after applying an ice pack to the site of anesthetic injection. METHODS: One hundred participants with traumatic finger injury were assessed. Digital nerve block was performed in fifty patients in the intervention group after 6 min of ice application. In the control group, this procedure was done without ice. The primary outcome was the difference between the needle stick and infiltration pain scores with and without ice pack. The secondary outcome the patient satisfaction score. The protocol of this study was approved by the Institutional Review Board, and it is registered in the Iranian Registry of Clinical Trials. RESULTS: The pain score was assessed using a Numeric Rating Scale. Both the needle skin and infiltration pain scores were statistically significantly lower in the intervention group (P < 0.001). The mean and median needle stick pain scores were 1.5 and 1.0 in the intervention group and 6.8 and 7.0 in the control group, respectively. Moreover, the mean and median infiltration pain scores were 2.7 and 2.0 in the intervention group and 8.5 and 9.0 in the control group, respectively. Patient satisfaction score was significantly higher in the intervention group. CONCLUSIONS: Ice pack is inexpensive, readily available, and is easy to apply. We recommend this method to reduce the injection pain before digital nerve block in the emergency department.

Developing a Checklist for Cardiopulmonary Resuscitation (CPR) Quality Control in Emergency Department; a Qualitative Study.

INTRODUCTION: Monitoring the quality of cardiopulmonary resuscitation (CPR) could help in achieving favorable outcomes, decreasing mortality, and preventing post-CPR neurologic sequels. This study aimed to generate a user-friendly checklist for CPR quality control in emergency department (ED). METHOD: A qualitative study was performed between January and December 2018. In the first step, two emergency medicine specialists searched currently available databases and extracted the factors related to CPR quality. Afterward, two sessions of focus group discussions were held. The participants included four emergency medicine specialists, two ED managers, one anesthesiologist, and one cardiologist. Subsequently, 20 medical specialists, consisting of 10 emergency medicine specialists, six anesthesiologists, and four cardiologists, were invited to a Delphi panel in order to rate the extracted items from the prior group discussions. RESULTS: During the two rounds of focus group discussions, 38 items related to the quality of CPR were identified. A Delphi panel evaluated the items; 31 items with at least 75% agreement were selected. These 31 items were included in the final checklist and after a pilot study and adjustment of its content they were sorted in 10 categories as follows: 1. chest compression, 2. airway, 3. bag-mask ventilation, 4. cardiac monitoring, 5. defibrillation, 6. intravenous (IV) drug delivery, 7. Medications, 8. Advanced airway, 9. CPR sequence, and 10. Reversible causes. CONCLUSION: Our study provides a checklist for monitoring the quality of CPR in ED, but it is still necessary to include other factors related to the ED environment on this checklist.

An Effective Method for Controlling Bleeding in a Ruptured Hepatic Hemangioma: A Case Report.

INTRODUCTION: Hepatic hemangioma is the most common benign tumor in the liver. Although intra-abdominal bleeding associated with its rupture is rare, but life-threatening. Here we report a case of ruptured hepatic hemangioma and applied method for controlling its bleeding. CASE REPORT: The patient was a 45-year-old man who was referred after crashing his motorcycle into a car. The patient's primary survey revealed intra-abdominal free fluid, but stable vital signs. Thirty minutes later, the patient's systolic blood pressure dropped to 85 mmHg. Laparotomy was performed a large hemangioma was observed involving almost the entire left lobe of the liver. Using a liver needle and 2-0 chromic suture, we entered the hemangioma at the perforation site of the lower portion of the liver and exit from the upper part. Then, we entered the upper part of the liver and exited from the lower part, and then it was tied. According to this approach, hemangioma was packed from the lower segment of the liver. CONCLUSION: In this case, the patient's abdomen was primarily closed without extra packing and embolization. The proposed method thus may be more effective compared to conventionally used methods.

Comparing the Therapeutic Effects of Dexamethasone-Metoclopramide with Ketorolac in Relieving Headache in Patients with Acute Migraine Attacks Presenting to the Emergency Department.

INTRODUCTION: Migraine is a frequent chief complaint of patients in the emergency department. A wide range of treatments are used for acute migraine. OBJECTIVE: This study aimed to compare the therapeutic effects of a combination of metoclopramide + dexamethasone with those of ketorolac for treatment of acute migraine in the emergency department. METHOD: This quasi-experimental study enrolled patients identified as migraine headache cases admitted to the emergency departments of Shohadaye Tajrish and Sina hospitals, Tehran, Iran. The patients were divided into two groups and treated with either 8 mg Dexamethasone + 10 mg Metoclopramide or 60 mg ketorolac, and then compared regarding the rate of pain control based on visual analogue scale (VAS) on arrival and 1 and 2 hours afterward. RESULTS: Overall, 86 patients were recruited, of whom 50 were male (58.1%). Their mean age was 37.6 ± 10.3 years. Thirty-five (40.7%) were in the ketorolac group and 51 (59.3%) were in the dexamethasone + metoclopramide group. Treatment success was defined as a reduction of at least 3 points in pain severity in comparison to the admission time. One hour after administration of medications, the reported pain intensity was 4.7 ± 2.0 and 6.2 ± 2.3 in ketorolac group and dexamethasone + metoclopramide group, respectively. By the second hour, pain intensity was 3.4 ± 1.2 and 2.9 ± 1.3 in ketorolac group and dexamethasone + metoclopramide group, respectively. The two groups did not show a significant difference in terms of the reported pain at this time (p= 0.04). CONCLUSION: Based on our findings, the pain reduction time was relatively shorter for ketorolac in acute migraine, but the final response was identical in the two groups.

Premedication With Midazolam or Haloperidol to Prevent Recovery Agitation in Adults Undergoing Procedural Sedation With Ketamine: A Randomized Double-Blind Clinical Trial.

STUDY OBJECTIVE: We evaluate the effect of midazolam and haloperidol premedication for reducing ketamine-induced recovery agitation in adult patients undergoing procedural sedation. We also compare physician satisfaction and recovery time. METHODS: We randomized emergency department patients older than 18 years who needed procedural sedation to receive 1 of the following 3 interventions in double-blind fashion 5 minutes before receiving intravenous ketamine at 1 mg/kg: intravenous distilled water, intravenous midazolam at 0.05 mg/kg, or intravenous haloperidol at 5 mg. Our main study outcomes were recovery agitation as assessed by the maximum observed Pittsburgh Agitation Scale score and by the Richmond Agitation-Sedation Scale score at 5, 15, and 30 minutes after ketamine administration. Our secondary outcomes were clinician satisfaction and recovery duration. RESULTS: We enrolled 185 subjects. The maximum Pittsburgh Agitation Scale score was significantly less with midazolam compared with placebo (difference 3; 95% confidence interval 1.27 to 4.72) and with haloperidol compared with placebo (difference 3; 95% confidence interval 1.25 to 4.75), and Richmond Agitation-Sedation Scale scores at 5, 15, and 30 minutes trended lower with the active agents. Midazolam and haloperidol significantly delayed recovery but did not alter overall clinician satisfaction. CONCLUSION: For adult procedural sedation, premedication with either midazolam 0.05 mg/kg or haloperidol 5 mg intravenously significantly reduces ketamine-induced recovery agitation while delaying recovery.

Modulation of the anticonvulsant effect of swim stress by agmatine.

Agmatine is an endogenous l-arginine metabolite with neuroprotective effects in the stress-response system. It exerts anticonvulsant effects against several seizure paradigms. Swim stress induces an anticonvulsant effect by activation of endogenous antiseizure mechanisms. In this study, we investigated the interaction of agmatine with the anticonvulsant effect of swim stress in mice on pentylenetetrazole (PTZ)-induced seizure threshold. Then we studied the involvement of nitric oxide (NO) pathway and endogenous opioid system in that interaction. Swim stress induced an anticonvulsant effect on PTZ seizures which was opioid-independent in shorter than 1-min swim durations and opioid-dependent with longer swims, as it was completely reversed by pretreatment with naltrexone (NTX) (10mg/kg), an opioid receptor antagonist. Agmatine significantly enhanced the anticonvulsant effect of opioid-independent shorter swim stress, in which a combination of subthreshold swim stress duration (45s) and subeffective dose of agmatine (1mg/kg) revealed a significantly higher seizure threshold compared with either one. This effect was significantly reversed by NO synthase inhibitor NG-nitro-l-arginine (L-NAME (Nω-Nitro-L-arginine methyl ester), 5mg/kg), suggesting an NO-dependent mechanism, and was unaffected by NTX (10mg/kg), proving little role for endogenous opioids in the interaction. Our data suggest that pretreatment of animals with agmatine acts additively with short swim stress to exert anticonvulsant responses, possibly by mediating NO pathway.

Intravenous caffeine citrate vs. magnesium sulfate for reducing pain in patients with acute migraine headache; a prospective quasi-experimental study.

BACKGROUND: Current evidence suggests that intravenous magnesium sulfate might be effective for reducing migraine pain. In a recent pilot study, we showed that intravenous caffeine citrate could reduce the severity of migraine headache. The objective of this study is to investigate the efficacy of intravenous caffeine citrate vs. magnesium sulfate for management of acute migraine headache. METHODS: We conducted a prospective quasi-experimental study from January until May 2016 in two educational medical centers of Shahid Beheshti University of Medical Sciences (Shoahadaye Tajrish Hospital and Imam Hossein Hospital), Tehran, Iran. The study included patients who were referred to the emergency department and met the migraine diagnosis criteria of the International Headache Society. Patients were allocated into 2 groups receiving either 60 mg intravenous caffeine or 2 g intravenous magnesium sulfate. The pain scores, based on the visual analog scale, were recorded on admission, as well as one and two hours after receiving the drug. A Chi-Square test and student t-test were used for analysis of baseline characteristics. A Mann-Whitney U test and Wilcoxon singed rank test were used to analyze differences in the visual analogue scale (VAS) score between and within the groups respectively. RESULTS: In total, 70 patients (35 patients in each group) with the mean age of 33.1 ± 11.3 years were included (64.3% female). For the Caffeine citrate group, the median pain score decreased from 9.0 (2.0) to 5.0 (4.0) after one hour and to 3.0 (4.0) after two hours. For the magnesium sulfate group, the pain score decreased from 8.0 (2.0) to 2.0 (2.0) after one hour and to 0.0 (1.0) after two hours. Both intravenous caffeine citrate and intravenous magnesium sulfate reduced pain scores significantly but the magnesium sulfate group showed more improvement than the Caffeine citrate group after one hour (P < 0.001) and after two hours (P < 0.001). CONCLUSIONS: It is likely that both intravenous caffeine and intravenous magnesium sulfate can reduce the severity of migraine headache. Moreover, intravenous magnesium sulfate at a dose of 2 g might be superior to intravenous caffeine citrate 60 mg for the short term management of migraine headache in emergency departments.

Head CT scan in Iranian minor head injury patients: evaluating current decision rules.

The objective of this study is to select one of the seven available clinical decision rules for minor head injury, for managing Iranian patients. This was a prospective cohort study evaluating medium- or high-risk minor head injury patients presenting to the Emergency Department. Patients with minor head trauma who were eligible for brain imaging based on seven available clinical decision rules (National Institute for Health and Clinical Excellence (NICE), National Emergency X-Radiography Utilization Study (NEXUS)-II, Neurotraumatology Committee of the World Federation of Neurosurgical Societies (NCWFNS), New Orleans, American College of Emergency Physicians (ACEP) Guideline, Scandinavian, and Canadian computed tomography (CT) head rule) were selected. Subjects were underwent a non-contrast axial spiral head CT scan. The outcome was defined as abnormal and normal head CT scan. Univariate analysis and stepwise linear regression were applied to show the best combination of risk factors for detecting CT scan abnormalities. Five hundred patients with minor head trauma were underwent brain CT scan. The following criteria were derived by stepwise linear regression: Glasgow Coma Scale (GCS) less than 15, confusion, signs of basal skull fracture, drug history of warfarin, vomiting more than once, loss of consciousness, focal neurologic deficit, and age over 65 years. This model has 86.15 % (75.33-93.45 %) sensitivity and 46.44 % (46.67-51.25 %) specificity in detecting minor head injury patients with CT scan abnormalities (95 % confidence interval). Of seven decision rules, only the Canadian CT Head Rule possesses seven of the eight high-risk factors associated with abnormal head CT results which were identified by this study. This study underlines the Canadian CT Head Rule's utility in Iranian minor head injury patients. Our study encourages researchers to evaluate available guidelines in different communities.