Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM)

Objective

To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI).

Participants

A multispecialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM).

Data sources

Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews.

Results

Three major pathophysiologic events were considered to constitute CIRCI: dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids. The dysregulation of the HPA axis is complex, involving multidirectional crosstalk between the CRH/ACTH pathways, autonomic nervous system, vasopressinergic system, and immune system. Recent studies have demonstrated that plasma clearance of cortisol is markedly reduced during critical illness, explained by suppressed expression and activity of the primary cortisol-metabolizing enzymes in the liver and kidney. Despite the elevated cortisol levels during critical illness, tissue resistance to glucocorticoids is believed to occur due to insufficient glucocorticoid alpha-mediated anti-inflammatory activity.

Conclusions

Novel insights into the pathophysiology of CIRCI add to the limitations of the current diagnostic tools to identify at-risk patients and may also impact how corticosteroids are used in patients with CIRCI.

     

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.

     

Phytomedicines in Acute Rhinosinusitis: A Prospective,Non-interventional Parallel-Group Trial

Introduction

The objective of this prospective, multicenter, parallel-group, non-interventional clinical trial (NIT) was to characterize the effectiveness of a treatment with the phytomedicines ELOM-080 and BNO 1016 in patients with acute rhinosinusitis (ARS).

Methods

A total of 228 patients suffering from ARS took part in this NIT and were treated for a maximum of 14 days with either BNO 1016 or ELOM-080. Focus was on improvement of rhinosinusitis-associated pain/discomfort and nasal congestion in real-life conditions of primary care setting, as assessed by numeric and verbal rating scale, and five-point Likert scale.

Results

The course of the key ARS symptom facial pain demonstrated a faster recovery in patients with ELOM-080, when compared to BNO 1016. ELOM-080 tended to be superior for several ancillary criteria and induced significantly higher patient satisfaction with regard to the improvement of feeling of general illness. Physicians assessed both products to be very effective and well tolerated. Adverse drug reactions classified as gastrointestinal disorders occurred in both groups to a comparable extent.

Conclusion

This trial demonstrated comparable effectiveness of a therapy of ARS with the phytomedicines ELOM-080 and BNO 1016, although the treatment with ELOM-080 resulted in a more rapid and more complete recovery in ARS key symptoms and tended to be superior for several ancillary criteria. Both treatments were well tolerated.

Trial registration number

NIS-6471.

Funding

G. Pohl-Boskamp GmbH & Co. KG.

     

Low dose quetiapine induced galactorrhoea: a case report

Background

Quetiapine causes less prolactin elevation and/or galactorrhoea than other atypical antipsychotics.

Case Presentation

Ms AB had galactorrhoea and raised prolactin levels at only 100 mg of quetiapine daily.

Conclusion

Low dose quetiapine can also cause galactorrhoea.

     

Création d’un programme d’éducation thérapeutique en douleur chronique (PETDC) — Expérience Canadienne

Aims

Create an educational program in chronic pain (EPCP).

Material and methods

We used a four-step process to create the EPCP tailored to patient’s needs.

Results

Five groups of patients can benefit from the program annually. Based on their own assessment, patients stated that their knowledge of chronic pain improved between 2.8 to 24%. The satisfaction with the EPCP was 8.67/10.

Conclusion

Our EPCP helps patients gain and maintain the skills they need to best manage their lives with a chronic pain.

     

Current and Emerging Treatment Modalities for Leber’s Hereditary Optic Neuropathy: A Review of the Literature

Introduction

The purpose of this review is to present the current and emerging treatment alternatives for Leber’s hereditary optic neuropathy (LHON), emphasizing the most recent use of idebenone and stem cells or gene therapy.

Methods

A comprehensive literature review was performed at the PubMed database regarding the various treatment modalities for LHON.

Results

Treatment modalities for LHON include nutritional supplements, activators of mitochondrial biogenesis, brimonidine, and symptomatic and supportive treatment, but nowadays attention is being paid to idebenone and gene therapy or stem cells.

Conclusion

The treatment of LHON remains challenging, given the nature of the disease and its prognosis.

     

Syncope and Headache

Purpose of Review

We review the literature on co-occurrence of syncope and headache and share clinical experience.

Recent Findings

Headache in relation to syncope has been the subject of recent interest.

Summary

Orthostatic intolerance has an expanding spectrum with three well-defined entities: orthostatic hypotension (OH), neurally mediated hypotension (NMH), and postural tachycardia syndrome (PoTS). Syncope occurs in patients with OH as well as in patients with episodically occurring NMH. Headache of OH is called coat-hanger ache (CHA) because it affects the neck and shoulders in a coat-hanger pattern. It can serve as a warning symptom of OH as well as a parameter to gauge the benefit of treatment. Awareness of CHA avoids inappropriate tests. Headache type occurring in NMH has not been fully delineated. A questionnaire-based study describes migraine leading to syncope and treatment of migraine to reduce syncope. Laboratory studies in NMH patients provide evidence for only short-duration headache. The author’s approach to such patients is presented.

     

Hemorrhagic shock from breast blunt trauma

Background

Seat belt use has been associated with decreased life-threatening thoracic injuries. However, there has been an increase in soft-tissue injuries such as breast trauma.

Case report

We describe a case of a young healthy female who presented to a community hospital Emergency department without any trauma designation following a motor vehicle accident. The patient was found to have hemorrhagic shock from an intramammary hemorrhage and was treated with blood products and a temporizing external abdominal binder in preparation for a transfer to a level 1 center where she was successfully treated with angiographic embolization.

Objectives

The objective of this study is to report on a case hemorrhagic shock from a breast hematoma as well as a review of the literature on previous seat belt associated breast trauma and its management in the emergency department.

Conclusion

Seat belt associated breast trauma is uncommon in the emergency medicine literature. However, it can be associated with life threatening intramammary bleeding. Emergency physicians should be aware of these injuries and their proper management.

     

Sekundäre Steife der Schulter

Background

In addition to idiopathic shoulder stiffness, secondary shoulder stiffness in particular is often associated with extra-articular subacromial adhesions between the rotator cuff and the surrounding anatomical structures.

Objective

The aim of this article is to present clinical results and complications as well as the surgical technique of extra-articular release in the context of secondary shoulder stiffness.

Material and Methods

Selective review of the literature and presentation of own clinical experience.

Results

Intra-articular and extra-articular release are related to a high patient satisfaction and an improved range of motion. Exact knowledge of the extra-articular anatomy is necessary to prevent iatrogenic lesions of vessels, nerves and the rotator cuff. Compared to patients with a primary stiff shoulder, patients suffering from posttraumatic stiff shoulder benefit more from arthroscopic interventions with intracapsular and extracapsular release.

Conclusion

Restrictions in range of motion of the shoulder can be related to extra-articular adhesions. These adhesions need to be specifically addressed during arthroscopic treatment of stiff shoulders.

     

« Kit KAD » (kit pour accompagner la douleur) — une collaboration territoriale réussie. Création d’une offre éducative pour patients douloureux chroniques

Introduction

Patients and care providers came up with the idea of an educational tool for patients with chronic pain

Methodology

The educational sessions were developed over a five-year period, with four meetings per year.

Results

“Kit KAD” answers the problems faced by patients in pain in everyday life. The “Kit KAD” offers tools and session leaders and can be used by any team trained in PTE (patient therapeutic education).

Conclusion

The “Kit KAD” group, assisted on methodology by the Eastern region UTEP (Transversal Patient therapeutic Education Unit), created an innovative educational tool for patients in chronic pain.

     

Influence of Antibiotic Pressure on Five Plasmid-based Bioluminescent Gram-negative Bacterial Strains

Purpose

The present study aims to develop five Gram-negative bacteria expressing bacterial luciferase for use to evaluate the influence of different antibiotics on bacterial bioluminescence.

Procedures

The pBBR-lux plasmid was introduced into five Gram-negative bacteria; the bioluminescent signals and colony-forming unit (CFU)/ml of all the bioluminescent strains were monitored with six antibiotics at various concentrations.

Results

Dose-dependent bioluminescence signals can be used for rapid bacterial antibiotic susceptibility test (AST). All five bioluminescent bacterial strains have similar bioluminescence and CFU enhancement at sub-minimum inhibitory concentration (MIC) of six different antibiotics.

Conclusion

The bioluminescent signals and CFU enhancement at sub-MIC antibiotic concentrations should be of value in the research of new antibiotic drugs and bioluminescent imaging.

     

Offene Arthrolyse des Kniegelenks

Background

Loss of range of motion of the knee joint causes significant disability. Surgical treatment should include arthroscopic as well as open arthrolysis procedures.

Objectives

Impairments of extension and flexion can have capsular or extra-articular origins in the musculature. The techniques of open capsulotomy and interventions on the proximal and distal extension apparatus are presented.

Methods

Discussion on the indications and surgical techniques for open arthrolysis of the knee joint are presented based on own results and the available literature.

Results

The established surgical techniques can significantly improve the range of motion considering the severity of this case group.

Conclusions

An exact analysis of the cause of knee stiffness is necessary. Only intra-articular problems can be arthroscopically treated and open techniques are indicated when the stiffness is caused by an extra-articular pathology. The techniques are established and reproducible.

     

Patienten mit chronischen Schmerzsyndromen

Background

The study was performed to reveal the effect of an individualized personal outpatient therapy program, based on a multidisciplinary assessment, on pain and health-related quality of life in patients with chronic pain.

Methods

Fifty patients were prospectively evaluated before and 3 months after establishment of an individualized outpatient therapy program. Health-related quality of life, pain and pain-related disability, depression and motivation to adopt self-management of chronic pain were assessed. Therapy adherence was tested with a structured interview.

Results

Only marginal improvements were observed in terms of pain and health-related quality of life. Therapy adherence varied between the different therapies.

Conclusions

An individualized personal outpatient therapy program has only marginal effects on pain and health-related quality of life in patients with chronic pain.

     

The effect of ultrasound with acoustic radiation force on rabbit lung tissue: a preliminary study

Purpose

Acoustic radiation force (ARF) elastography has recently become available. The previous animal studies have revealed lung injuries induced by diagnostic ultrasound, but the effects on the lung resulting from exposure to ultrasound with ARF are unknown. This study aimed to assess the risk of lung injury associated with ultrasound with ARF.

Methods

A focused 2.5-MHz transducer that emits ultrasound with ARF was used. A rabbit was anesthetized, and the transducer was placed in the right subcostal region. Exposure settings of mechanical index (MI) 0.80, pulse duration 10 ms, pulse repetition time 5 s, and exposure time 150 s were applied.

Results

One red spot (7 × 6 mm) was observed on the surface of the right lung corresponding to the area of exposure. Alveolar hemorrhage was observed microscopically. This lesion was visible across a range of 20–170 μm in depth from the pleural surface.

Conclusion

The first example of lung hemorrhage induced by ultrasound with ARF was observed in this study. This observation suggests the possibility of lung injury in humans when ARF elastography is applied with the transducer directed toward the lung. Further studies are needed to determine the safety of this modality.

     

Predictive factors for polypharmacy among child and adolescent psychiatry inpatients

Background

Aim was to determine the predictive factors for polypharmacy among inpatient children and adolescents with psychiatric disorders.

Methods

Blinded, case-note review of children and adolescents with ICD 10 diagnosis of psychiatric disorders on psychotropic medication was conducted. Data on demography, illness, and treatment was analyzed with univariate and multivariate techniques.

Results

Proscribing non-pharmacological interventions (OR = 4.7) and pro re nata medication (OR = 3.3), increased the risk of polypharmacy. Prescribing physical restraint reduced the risk of receiving multiple medications (OR = 0.3).

Conclusion

Proscribing non-pharmacological interventions, pro re nata medication and physical restraints increased polypharmacy.

     

Nasal continuous positive airway pressure decreases respiratory muscles overload in young infants with severe acute viral bronchiolitis

Objective

To determine the efficacy of nasal continuous positive airway pressure (nCPAP) on respiratory distress symptoms and respiratory effort in young infants with acute respiratory syncytial virus bronchiolitis.

Design

Prospective study.

Setting

The paediatric intensive care unit of a university hospital.

Patients

Twelve infants less than 3 months of age, with severe respiratory distress.

Interventions

Respiratory distress was quantified with a specific scoring system. Oesophageal pressure (Pes) was measured during spontaneous ventilation before and after nCPAP, delivered through an infant-adapted ventilator. Simultaneous recording of gastric pressure (Pgas) was performed in the five oldest patients.

Measurements and results

The respiratory distress score decreased after nCPAP, particularly accessory muscles’ use and expiratory wheezing. The breathing pattern was modified, with shorter inspiratory and longer expiratory time. Pes swings and PTPes_insp, two indices of inspiratory effort, were reduced by 54 (±4)% and 59 (±5)%. PTPgas_exp, an indicator of expiratory muscles activity, was completely abolished. A significant correlation was observed between the respiratory distress score and Pes swings at baseline and after nCPAP.

Conclusions

In young infants with severe acute respiratory syncytial virus bronchiolitis, nCPAP rapidly unloads respiratory muscles and improves respiratory distress symptoms.

     

Determination of a cutoff attenuation value on single-phase contrast-enhanced CT for characterizing adrenal nodules via chemical shift MRI

Purpose

This study aims to determine the optimal cutoff attenuation value on single-phase contrast-enhanced CT (CECT) at which chemical shift MRI (CSMRI) yields sufficient accuracy to replace the standard CT adrenal protocol for the diagnosis of adrenal adenomas.

Methods

Between January 2010 and December 2014, a total of 49 patients (age: 20–81 years; 23 men and 26 women) with 60 adrenal tumors (48 adenomas and 12 non-adenomas) who underwent both CECT in portal venous phase and CSMRI were included in the study. Attenuation on portal venous phase CECT, adrenal-to-spleen chemical shift ratio (ASR), and signal-intensity index (SII) were obtained for each adrenal mass.

Results

Among different cutoff values on CECT (from <70 to <120 HU), the diagnostic accuracies for those lesions measuring <80 HU were the highest and most similar to dedicated adrenal CT. The sensitivities and specificities of SII were up to 96% (25/26) and 100% (7/7) for those measuring <80 HU, but reduced to 73% (16/22) and 80% (4/5) for those ≥80 HU. The overall sensitivities and specificities for diagnosing adrenal adenoma using SII vs. ASR were 85% (41/48) and 92% (11/12) vs. 71% (34/48) and 100% (12/12), respectively.

Conclusions

CSMRI may replace CT adrenals in the work-up of patients with adrenal nodules below 80 HU on single-phase CECT, hence reducing radiation exposure and iodinated contrast administration. Adrenal nodules greater than 80 HU cannot be accurately diagnosed by CSMRI. CT adrenal protocol remains the appropriate investigative modality in those cases.

     

Anonymisieren oder personalisieren?

Background

The subjective state of health with respect to pain and psyche was surveyed utilizing validated pain questionnaires in patients undergoing special pain therapy and represents the basis for targeted treatment measures.

Objective

The purpose of this study was to investigate the possible distortion of answers due to social desirability of responses in chronic pain patients.

Material and methods

During two survey periods assessing patient satisfaction using both anonymized and personalized questionnaires, the effects arising from socially desirable response patterns were analyzed. The sample consisted of chronic pain patients being treated in an inpatient therapy setting.

Results

In both periods of observation no significant impact on the response behavior of chronic pain patients was found in personalized or anonymized questionnaires.

Conclusion

The results of the study suggest that the responses of chronic pain patients with respect to their subjective state of health are not influenced by social desirability. Thus, scoring systems such as the German pain questionnaire will not be influenced by social desirability in chronic pain patients and can therefore be used as a part of diagnostics and therapy planning.

     

Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data

Introduction

Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(?) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods

The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results

At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions

These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(?) B-precursor ALL compared with salvage chemotherapy.

Funding

Amgen.

Trial Registration

ClinicalTrials.gov identifier NCT01466179 and NCT02003612.