The rate of brain death and organ donation in patients resuscitated from cardiac arrest: a systematic review and meta-analysis

Background

The occurrence of brain death in patients with hypoxic-ischaemic brain injury after resuscitation from cardiac arrest creates opportunities for organ donation. However, its prevalence is currently unknown.

Methods

Systematic review. MEDLINE via PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews were searched for eligible studies (2002–2016). The prevalence of brain death in adult patients resuscitated from cardiac arrest and the rate of organ donation among brain dead patients were summarised using a random effect model with double-arcsine transformation. The quality of evidence (QOE) was evaluated according to the GRADE guidelines.

Results

26 studies [16 on conventional cardiopulmonary resuscitation (c-CPR), 10 on extracorporeal CPR (e-CPR)] included a total of 23,388 patients, 1830 of whom developed brain death at a mean time of 3.2 ± 0.4 days after recovery of circulation. The overall prevalence of brain death among patients who died before hospital discharge was 12.6 [10.2–15.2] %. Prevalence was significantly higher in e-CPR vs. c-CPR patients (27.9 [19.7–36.6] vs. 8.3 [6.5–10.4] %; p < 0.0001). The overall rate of organ donation among brain dead patients was 41.8 [20.2–51.0] % (9/26 studies, 1264 patients; range 0–100 %). The QOE was very low for both outcomes.

Conclusions

In patients with hypoxic-ischaemic brain injury following CPR, more than 10 % of deaths were due to brain death. More than 40 % of brain-dead patients could donate organs. Patients who are unconscious after resuscitation from cardiac arrest, especially when resuscitated using e-CPR, should be carefully screened for signs of brain death.

     

Venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock post-cardiac arrest

Purpose

To describe the characteristics, outcomes, and risk factors associated with poor outcome of venoarterial extracorporeal membrane oxygenation (VA-ECMO)-treated patients with refractory shock post-cardiac arrest.

Methods

We retrospectively analyzed data collected prospectively (March 2007–January 2015) in a 26-bed tertiary hospital intensive care unit. All patients implanted with VA-ECMO for refractory cardiogenic shock after successful resuscitation from cardiac arrest were included. Refractory cardiac arrest patients, given VA-ECMO under cardiopulmonary resuscitation, were excluded.

Results

Ninety-four patients received VA-ECMO for refractory shock post-cardiac arrest. Their hospital and 12-month survival rates were 28 and 27 %, respectively. All 1-year survivors were cerebral performance category 1. Multivariable analysis retained INR >2.4 (OR 4.9; 95 % CI 1.4–17.2), admission SOFA score >14 (OR 5.3; 95 % CI 1.7–16.5), and shockable rhythm (OR 0.3; 95 % CI 0.1–0.9) as independent predictors of hospital mortality, but not SAPS II, out-of-hospital cardiac arrest score, or other cardiac arrest variables. Only 10 % of patients with an admission SOFA score >14 survived, whereas 50 % of those with scores ≤14 were alive at 1 year. Restricting the analysis to the 67 patients with out-of-hospital cardiac arrest of coronary cause yielded similar results.

Conclusion

Among 94 patients implanted with VA-ECMO for refractory cardiogenic shock post-cardiac arrest resuscitation, the 24 (27 %) 1-year survivors had good neurological outcomes, but survival was significantly better for patients with admission SOFA scores <14, shockable rhythm, and INR ≤2.4. VA-ECMO might be considered a rescue therapy for patients with refractory cardiogenic shock post-cardiac arrest resuscitation.

     

Targeted temperature management after intraoperative cardiac arrest: a multicenter retrospective study

Purpose

Few outcome data are available about temperature management after intraoperative cardiac arrest (IOCA). We describe targeted temperature management (TTM) (32–34 °C) modalities, adverse events, and association with 1-year functional outcome in patients with IOCA.

Methods

Patients admitted to 11 ICUs after IOCA in 2008–2013 were studied retrospectively. The main outcome measure was 1-year functional outcome.

Results

Of the 101 patients [35 women and 66 men; median age, 62 years (interquartile range, 42–72)], 68 (67.3%) were ASA PS I to III and 57 (56.4%) had emergent surgery. First recorded rhythms were asystole in 44 (43.6%) patients, pulseless electrical activity in 36 (35.6%), and ventricular fibrillation/tachycardia in 20 (19.8%). Median times from collapse to cardiopulmonary resuscitation and return of spontaneous circulation (ROSC) were 0 min (0–0) and 10 min (4–20), respectively. The 30 (29.7%) patients who received TTM had an increased risk of infection (P = 0.005) but not of arrhythmia, bleeding, or metabolic/electrolyte disorders. By multivariate analysis, one or more defibrillation before ROSC was positively associated with a favorable functional outcome at 1-year (OR 3.06, 95% CI 1.05–8.95, P = 0.04) and emergency surgery was negatively associated with 1-year favorable functional outcome (OR 0.36; 95% CI 0.14–0.95, P = 0.038). TTM use was not independently associated with 1-year favorable outcome (OR 0.82; 95% CI 0.27–2.46, P = 0.72).

Conclusions

TTM was used in less than one-third of patients after IOCA. TTM was associated with infection but not with bleeding or coronary events in this setting. TTM did not independently predict 1-year favorable functional outcome after IOCA in this study.

     

Successful resuscitation for cardiac arrest due to severe accidental hypothermia accompanied by mandibular rigidity: a case of cold stiffening mimicking rigor mortis

Background

In cases of severe accidental hypothermia, it was recommended that resuscitation should be continued until the patient has rewarmed, as hypothermia itself can preserve cerebral function, and hypothermic cardiac arrest is reversible. During cardiopulmonary resuscitation for normothermic patients, muscle rigidity suggests the initiation of postmortem changes such as rigor mortis and can lead to the termination of resuscitation. Currently, the prognosis of cardiac arrest due to severe accidental hypothermia accompanied by rigidity is unknown.

Case presentation

A 29-year-old woman was found unresponsive near a snowy mountain trail. Upon discovery, she was found to be in cardiac arrest with an initial asystole rhythm and exhibited mandibular rigidity. On admission, her core temperature was 22 °C. Although cardiac arrest continued, and she showed no response to normal resuscitation, blood gas analysis revealed that her initial serum potassium level was 5.4 mmol/L. Extracorporeal membrane oxygenation (ECMO) for systemic perfusion and rewarming was initiated. After ECMO was introduced, return of spontaneous circulation was achieved. She showed no neurological impairments at discharge.

Conclusions

Muscle rigidity does not rule out the possibility of resuscitation in patients with severe accidental hypothermia under cardiac arrest. Serum potassium levels may assist in deciding whether ECMO should be introduced, even if a patient is in asystole. This knowledge may help emergency physicians to save the lives of such patients.

     

Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial

Purpose

We aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury.

Methods

In the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 2³ factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65–75 mmHg) vs. high-normal (80–100 mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6 months after cardiac arrest.

Results

We recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p?<?0.001). The median (interquartile range) NSE concentration at 48 h was 20.6 µg/L (15.2–34.9 µg/L) in the low-normal MAP group and 22.0 µg/L (13.6–30.9 µg/L) in the high-normal MAP group, p?=?0.522. We found no differences in the secondary outcomes.

Conclusions

Targeting a specific range of MAP was feasible during post-resuscitation intensive care. However, the blood pressure level did not affect the NSE concentration at 48 h after cardiac arrest, nor any secondary outcomes.

     

Organ support therapy in the intensive care unit and return to work: a nationwide,register-based cohort study

Purpose

The association between severity of illness and ability to return to work is unclear. Therefore, we investigated return to work and associations with measures of illness severity in ICU survivors.

Methods

We conducted this cohort study using Danish registry data for the period 2005–2014 on ICU patients who were discharged alive from hospital, had an ICU length of stay (LOS) of at least 72 h, were not treated with dialysis before hospital admission and were working prior to admission. We assessed (1) the cumulative incidence (chance) of return to work (2005–2017) and receipt of social benefits after discharge from a hospital stay with ICU admission and (2) the association between organ support therapies (renal replacement therapy, cardiovascular support and mechanical ventilation), and during 2011–2014 SAPS II and ICU LOS, and return to work, using multivariable Cox regression.

Results

Among 5762 ICU survivors, 68% returned to work within 2 years after hospital discharge. Disability and sickness benefits constituted 89% of social benefits among patients not returning to work and 59% among patients withdrawing from work following an initial return to work. Mechanical ventilation (HR 0.70, 95% CI [0.65–0.77]), but not RRT (HR 0.85, 95% CI [0.71–1.02]), cardiovascular support (HR 0.93, 95% CI [0.82–1.07]) and increasing SAPS II, was associated with decreased chance of return to work. Increasing ICU LOS was also associated with a decreased chance of return to work.

Conclusions

The majority of a nationwide cohort of ICU survivors returned to work. Sick leave and receipt of disability pension were common following ICU admission. Mechanical ventilation and longer ICU LOS were associated with reduced chances of return to work.

     

Pooled Aquablation Results for American Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in Large Prostates (60–150 cc)

Introduction

To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.

Methods

Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).

Results

One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Q_max increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.

Conclusion

Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.

Trial Registration

ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.

Funding

PROCEPT BioRobotics.

     

Does severe obstructive sleep apnea syndrome alter retrobulbar blood flow? A color Doppler ultrasound study

Purpose

To evaluate extraocular orbital vessels with color Doppler ultrasound (CDU) and investigate the effects of severe obstructive sleep apnea (OSA) on retrobulbar blood flow.

Methods

Between February 2014 and September 2015, 30 patients with severe OSA (apnea–hypopnea index (AHI) > 30) and 28 controls were prospectively included in this study. Intraocular pressure (IOP) was measured with a Goldmann applanation tonometer, and CDU was used to evaluate the retrobulbar vessels.

Results

The mean AHI score for the OSA group was 63.2 ± 21.5 per hour. The IOP values were significantly higher in the severe OSA group (p < 0.05). The central retinal artery peak systolic velocity (PSV) (p < 0.05) and end-diastolic velocity (EDV) (p < 0.02), and the ophthalmic artery (OA) PSV and EDV, were found to be significantly lower in the OSA group (p < 0.05).

Conclusion

Severe OSA causes an increase in IOP and a decrease in flow velocity in the retrobulbar circulation.

     

Extracorporeal life support during cardiac arrest and cardiogenic shock: a systematic review and meta-analysis

Purpose

Veno-arterial extracorporeal life support (ECLS) is increasingly used in patients during cardiac arrest and cardiogenic shock, to support both cardiac and pulmonary function. We performed a systematic review and meta-analysis of cohort studies comparing mortality in patients treated with and without ECLS support in the setting of refractory cardiac arrest and cardiogenic shock complicating acute myocardial infarction.

Methods

We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed updated to December 2015. Thirteen studies were included of which nine included cardiac arrest patients (n = 3098) and four included patients with cardiogenic shock after acute myocardial infarction (n = 235). Data were pooled by a Mantel-Haenzel random effects model and heterogeneity was examined by the I ² statistic.

Results

In cardiac arrest, the use of ECLS was associated with an absolute increase of 30 days survival of 13 % compared with patients in which ECLS was not used [95 % CI 6–20 %; p < 0.001; number needed to treat (NNT) 7.7] and a higher rate of favourable neurological outcome at 30 days (absolute risk difference 14 %; 95 % CI 7–20 %; p < 0.0001; NNT 7.1). Propensity matched analysis, including 5 studies and 438 patients (219 in both groups), showed similar results. In cardiogenic shock, ECLS showed a 33 % higher 30-day survival compared with IABP (95 % CI, 14–52 %; p < 0.001; NNT 13) but no difference when compared with TandemHeart/Impella (?3 %; 95 % CI ?21 to 14 %; p = 0.70; NNH 33).

Conclusions

In cardiac arrest, the use of ECLS was associated with an increased survival rate as well as an increase in favourable neurological outcome. In the setting of cardiogenic shock there was an increased survival with ECLS compared with IABP.

     

Short cervix detection in pregnant women by transabdominal sonography with post-void technique

Purpose

This study aimed to evaluate the diagnostic properties of transabdominal sonography with the post-void technique for cervical length measurement.

Methods

This study was a prospective cohort study. The inclusion criteria were pregnant women aged 18–40 years with gestational age of 18–23 completed weeks. Transabdominal sonography with vertical bladder depth of less than 5 cm and transvaginal cervical length measurements were carried out by a single experienced sonographer.

Results

There were 307 eligible pregnant women. The mean age of all subjects was 29.0 years. The mean cervical length obtained through transabdominal and transvaginal measurement was 3.33 and 3.47 cm, respectively. Ten patients (3.3 %) were identified as having a short cervix using transvaginal sonography, and 12 patients (3.9 %) were identified using transabdominal sonography.

Conclusion

Transabdominal sonography with vertical bladder depth of less than 5 cm performed better compared with transvaginal sonography. It may not be necessary to perform transvaginal sonography if transabdominal sonography reveals the cervical length to be more than 2.5 cm.

     

Pharmacokinetics of a Single Dose of Azilsartan in Pediatric Patients: A Phase 3, Open-Label,Multicenter Study

Introduction

Azilsartan is an angiotensin II receptor blocker indicated for the treatment of patients with hypertension. The efficacy and safety of azilsartan are established in adults, but have not been evaluated in pediatric patients, nor has its pharmacokinetic profile been determined in pediatric patients.

Methods

In this phase 3, open-label, multicenter study, we investigated the pharmacokinetics and safety of single doses of azilsartan in six Japanese patients with hypertension, aged 9–14 years. The dose of azilsartan was 5 mg for three patients weighing less than 50 kg, with mean body weight at baseline of 27.5 kg, and 10 mg for three patients weighing at least 50 kg, with mean body weight at baseline of 65.9 kg.

Results

Mean maximum plasma concentration (C_max) of azilsartan was 888.3 and 831.3 ng/mL and median time to maximum concentration (T_max) of unchanged azilsartan was 3.0 and 4.0 h, in the 5-mg and 10-mg groups, respectively. Mean areas under the plasma concentration–time curve (AUC) from 0–24 h post-dose (AUC_0–24) and 0 h to infinity (AUC_0–inf) were 6350.3 and 6635.7 ng h/mL, respectively, in the 5-mg group, and 6871.7 and 7433.3 ng h/mL, respectively, in the 10-mg group. Both doses were well tolerated; no treatment-emergent adverse events considered to be related to azilsartan occurred during the study.

Conclusion

Our data suggest that pediatric patients weighing less than 50 kg may have? approximately 2-fold greater exposure to azilsartan than those weighing at least 50 kg at the same dose. Exposure to azilsartan in children weighing at least 50 kg is comparable to that in healthy adults at the same dose.

Trial Registration

ClinicalTrials.gov identifier, NCT02451150.

Funding

Takeda Pharmaceutical Co. Ltd.

     

A review of mallet finger and jersey finger injuries in the athlete

Purpose of review

The purposes of this review are to discuss the diagnosis and management of mallet and jersey finger injuries in athletes and to highlight how treatment impacts return to play.

Recent findings

Mallet finger: although numerous non-operative and operative techniques have been described, there continues to be little consensus regarding the optimal procedure. Jersey finger: ultrasound appears to be a cost-effective imaging modality that may be useful for preoperative planning. Wide-awake surgery offers optimal intraoperative assessment of the tendon repair. Tendon repair with volar plate augmentation has been shown to improve the strength of the repair in the laboratory, and early clinical results are encouraging.

Summary

Most mallet finger injuries will heal with non-operative treatment over a period of 8–12 weeks, even when treatment is delayed up to 3–4 months. An acute diagnosis of jersey finger requires surgical treatment and generally means 8–12 weeks of inability to compete in most contact sports.

     

Outcomes Following Implantation of Two Second-Generation Trabecular Micro-Bypass Stents in Patients with Open-Angle Glaucoma on One Medication: 18-Month Follow-Up

Introduction

The study objective was to evaluate the intraocular pressure (IOP) and medication-lowering effect of 2 second-generation trabecular micro-bypass stents in eyes with open-angle glaucoma (OAG) on one preoperative medication.

Methods

Fifty-seven qualified phakic eyes with OAG on 1 medication, preoperative medicated IOP of 18–30 mmHg, and preoperative unmedicated (post-washout) IOP of 22–38 mmHg underwent implantation of 2 second-generation trabecular micro-bypass stents in a standalone procedure. Evaluations included IOP, best-corrected visual acuity, medication use, fundus and slit lamp examinations, visual field, cup to disc ratio, pachymetry, and complications and interventions. Subjects have been followed for 18 months, and follow-up is ongoing.

Results

At Month 12 postoperative, 100% of eyes had achieved an IOP reduction ≥20% (100% had IOP ≤18 mmHg and 67% had IOP ≤15 mmHg) without medication versus preoperative unmedicated IOP, and 75% had IOP reduction ≥20% without medication versus preoperative medicated IOP. The Month 12 mean unmedicated IOP had decreased by 42%, to 14.2 ± 1.9 mmHg vs 24.4 ± 1.3 mmHg preoperatively, and this reduction was maintained through 18 months (14.4 ± 2.1 mmHg). A high safety profile was observed.

Conclusion

In this prospective, open-label, single-arm study, the standalone implantation of two second-generation trabecular micro-bypass stents in OAG patients on 1 preoperative medication resulted in IOP reduction to ≤15 mmHg and elimination of medication through 18 months, with favorable safety.

Trial Registration

ClinicalTrials.gov identifier, NCT02868190.

Funding

Glaukos Corporation, San Clemente, CA.

     

Factors and Regional Differences Associated with Endometriosis: A Multi-Country,Case–Control Study

Introduction

The present study aimed to investigate clinical, lifestyle, and environmental factors associated with endometrioma (OMA) and/or deep infiltrating endometriosis (DIE) as determined by case–control comparison [women with superficial peritoneal endometriosis (SUP) or no endometriosis], and compare differences between factor associated with endometriosis at a national level.

Methods

This was three countries (China, Russia, and France), case–control study in 1008 patients. Patients were identified and enrolled during their first routine appointment with their physician post-surgery for a benign gynecologic indication, excluding pregnancy. Retrospective information on symptoms and previous medical history was collected via face-to-face interviews; patients also completed a questionnaire to provide information on current habits. For every DIE patient recruited (n = 143), two women without endometriosis (n = 288), two SUP patients (n = 288), and two OMA patients (n = 288) were recruited.

Results

For the overall population, factors significantly associated (P ≤ 0.05) with DIE or OMA [Odds ratio (OR) >1] were: previous use of hormonal treatment for endometriosis [OR 6.66; 95% confidence interval (CI) 4.05–10.93]; previous surgery for endometriosis (OR 1.95; 95% CI 1.11–3.43); and living or working in a city or by a busy area (OR 1.66; 95% CI 1.09–2.52). Differences between regions with regard to the diagnosis, symptomatology, and treatment of endometriosis exist.

Conclusion

The findings provide insight into potential risk factors for endometriosis and differences between regions in terms of endometriosis management and symptomatology. Further investigations are required to confirm the associations found in this study.

Trial registration

ClinicalTrials.gov identifier, NCT01351051.

Funding

Ipsen.

     

Comparison of quality of chest compressions during training of laypersons using Push Heart and Little Anne manikins using blinded CPRcards

Background

Mass Cardio-Pulmonary Resuscitation (CPR) training using less expensive and easily portable manikins is one way to increase the number of trained laypeople in a short time. The easy-to-carry, low-cost CPR training model called Push Heart (PH) is widely used in Japan. The aim of this study was to examine if PH can achieve chest compression quality that is similar to that using more conventional Little Anne (LA) manikins for training laypersons.

Methods

This prospective randomized crossover study was done during routine community CPR training of laypersons in Singapore. The participants were randomly allocated into two groups, using the PH and LA models respectively. They crossed over during the training so that both groups had measurements using both models. Chest compression data were collected using blinded CPRcards, which are credit card-sized devices with accelerometers and data capture. Participants did not receive any CPR feedback during measurement.

Results

Forty-two people had data captured for the study with 15 males. The median compression depth was 41.5 mm on LA and 38.0 mm on PH (p?=?0.0664), and median compression rate was 105 cpm on LA and 103 cpm on PH (p?=?0.2429). Overall, only 1.5% of compressions performed on the PH achieved adequate depth of between 50–70 mm compared to 5.5% achieved on LA (p?=?0.049). In contrast, 84% of all compressions performed on the PH were within the adequate rate of 100–120 cpm compared to 79.5% on LA (p?=?0.457). Only the under 20-year-old group was able to achieve adequate median compression depth (50.5 mm) on LA, while the older age groups did not (p?=?0.0024). The other age groups performed similar quality of chest compression regardless of the model used. 73.8% of participants preferred the LA for training. After the training, participants felt similarly well-prepared with either model with a median score of 8/10 on LA compared to 7/10 on PH (p?=?0.0011).

Conclusions

The PH can be an alternative mass CPR training model. Both models achieved satisfactory chest compression rates, but the majority of participants, especially the elderly, had difficulty achieving adequate depth.

     

Gallium-68 Complexes Conjugated to Pittsburgh Compound B: Radiolabeling and Biological Evaluation

Purpose

The aim of this work is to develop an efficient and fully automated radiosynthesis of three derivatives of the Pittsburgh compound B labeled with gallium-68 for the detection of amyloid plaques.

Procedures

The radiolabeling of the precursors and purification of the radiolabeled agents by high pressure liquid chromatography has been studied prior to their in vitro and in vivo evaluations.

Results

The complete process led, in 50 min, to pure Ga-68 products in a 12–38 % yield and with appreciable specific radioactivity (SRA, 85–168 GBq/μmol) which enabled us to demonstrate a considerable in vivo stability of the products. Unfortunately, this result was associated with a poor blood–brain barrier (BBB) permeability and a limited uptake of our compounds by amyloid deposits was observed by in vitro autoradiography.

Conclusion

Although we have not yet identified a compound able to significantly mark cerebral amyloidosis, this present investigation will likely contribute to the development of more successful Ga-68 radiotracers.

     

Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody Positivity and Disease Activity in Established Rheumatoid Arthritis: Findings from a US Observational Cohort

Introduction

To assess the relationship between low bone mineral density (BMD), anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity in patients with established rheumatoid arthritis (RA).

Methods

Patients enrolled in a single-center, observational cohort registry of patients with RA. Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR–BMD), and anti-CCP2 antibody measurements at the same time point or within 6 months. Anti-CCP2–immunoglobulin (Ig)G-positive (+) patients (≥ 20 U/mL) were distributed into three equal groups (Gp1–3), representing increasing anti-CCP2 antibody concentrations. Associations between BMD and anti-CCP2 antibody status and titer were explored in multivariate regression analyses controlling for covariates (including age, duration of RA, use of steroids, use of osteoporosis medication). Association between disease activity (DAS28 [CRP] < 2.6) and bone loss was also explored.

Results

A total of 149 patients (all women) were included (47 anti-CCP2 antibody negative [?], 102 anti-CCP2+ [34\titer group]). Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti-CCP2? group. DXR–BMD was lower in the anti-CCP2+ vs. the anti-CCP2? groups (Gp1–3 vs. anti-CCP2?: P < 0.0001 for left and right hands). DXR–BMD decreased with increasing anti-CCP2 titer (P < 0.001 for left and right hands). Patients with low DXR–BMD were less likely to have a DAS28 (CRP) < 2.6 (P = 0.0181).

Conclusion

Among patients with established RA, data suggest that anti-CCP2+ patients, particularly those with high anti-CCP2 antibody titers, have lower hand BMD, and patients with lower hand BMD are less likely to have low disease activity.

Funding

Bristol-Myers Squibb.

Trial Registration

Clinicaltrials.gov identifier, NCT01793103.

     

Characteristics and outcome for admissions to adult,general critical care units with acute severe asthma: a secondary analysis of the ICNARC Case Mix Programme Database

Introduction

This report describes the case mix, outcome and activity (duration of intensive care unit [ICU] and hospital stay, inter-hospital transfer, and readmissions to the ICU) for admissions to ICUs for acute severe asthma, and investigates the effect of case mix factors on outcome.

Methods

We conducted a secondary analysis of data from a high-quality clinical database (the Intensive Care National Audit and Research Centre [ICNARC] Case Mix Programme Database) of 129,647 admissions to 128 adult, general critical care units across England, Wales and Northern Ireland over the period 1995–2001.

Results

Asthma accounted for 2152 (1.7%) admissions, and in 57% mechanical ventilation was employed during the first 24 hours in the ICU. A total of 147 (7.1%) patients died in intensive care and 199 (9.8%) died before discharge from hospital. The mean age was 43.6 years, and the ratio of women to men was 2:1. Median length of stay was 1.5 days in the ICU and 8 days in hospital. Older age, female sex, having received cardiopulmonary resuscitation (CPR) within 24 hours before admission, having suffered a neurological insult during the first 24 hours in the ICU, higher heart rate, and hypercapnia were associated with greater risk for in-hospital death after adjusting for Acute Physiology and Chronic Health Evaluation II score. CPR before admission, neurological insult, hypoxaemia and hypercapnia were associated with receipt of mechanical ventilation after adjusting for Acute Physiology and Chronic Health Evaluation II score.

Conclusion

ICU admission for asthma is relatively uncommon but remains associated with appreciable in-hospital mortality. The greatest determinant of poor hospital survival in asthma patients was receipt of CPR within 24 hours before admission to ICU. Clinical management of these patients should be directed at preventing cardiac arrest before admission.

     

Olanzapine vs haloperidol: treating delirium in a critical care setting

Objective

To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.

Design

Prospective randomized trial

Setting

Tertiary care university affiliated critical care unit.

Patients

All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.

Interventions

Patients were randomized to receive either enteral olanzapine or haloperidol.

Measurements

Patient’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.

Main results

Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.

Conclusions

Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.