Malignant hyperthermia 2020: Guideline from the Association of Anaesthetists.

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.

A systematic review of phenylephrine vs. noradrenaline for the management of hypotension associated with neuraxial anaesthesia in women undergoing caesarean section.

Phenylephrine is recommended for the management of hypotension after spinal anaesthesia in women undergoing caesarean section. Noradrenaline, an adrenergic agonist with weak ß-adrenergic activity, has been reported to have a more favourable haemodynamic profile than phenylephrine. However, there are concerns that noradrenaline may be associated with a higher risk of fetal acidosis, defined as an umbilical artery pH < 7.20. We performed a systematic review of trials comparing noradrenaline with phenylephrine, concentrating on primary outcomes of fetal acidosis and maternal hypotension. We identified 13 randomised controlled trials including 2002 patients. Heterogeneity among the studies was high, and there were too few data to calculate a pooled effect estimate. Fetal acidosis was assessed in four studies that had a low risk of bias and a low risk of confounding, that is, studies which used a prophylactic vasopressor and where women received the allocated vasopressor only. There were no significant differences between these studies. No significant differences were observed for hypotension. Two trials found a significantly lower incidence of bradycardia when using noradrenaline. Cardiac output was significantly higher after noradrenaline in two of three studies. For other secondary outcomes including nausea, vomiting and Apgar scores at 1 and 5 min, no studies found significant differences. The evidence so far is too limited to support an advantage of noradrenaline over phenylephrine. Concerns of a deleterious effect of noradrenaline on fetal blood gas status cannot currently be assuaged by the available data from randomised controlled studies.

Generalisability of randomised trials of the programmed intermittent epidural bolus technique for maintenance of labour analgesia: a prospective single centre cohort study.

BACKGROUND: Several randomised controlled trials show that maintenance of labour epidural analgesia with programmed intermittent epidural bolus reduces the maternal motor block compared with maintenance with a continuous infusion. However, these trials were usually restricted to healthy nulliparous parturients. To assess the generalisability of these randomised controlled trials to 'real-world' conditions, we compared maternal motor function (modified Bromage score) over time between healthy nulliparous and parous women using routinely collected quality-control data. METHODS: After ethical approval, all parturients receiving programmed intermittent epidural bolus labour analgesia between June 2013 and October 2014 were included in this prospective cohort study. Bupivacaine 0.1% with fentanyl 2 µg ml-1 was used allowing for patient-controlled bolus every 20 min. The maternal motor function (primary outcome) was regularly assessed from insertion of the epidural catheter until delivery. RESULTS: Of the 839 parturients included, 553 (66%) were nulliparous and 286 (34%) were parous. The parous women had a shorter median duration of epidural analgesia (3 h 59 min vs 5 h 45 min) and a higher incidence of spontaneous delivery (66% vs 37%). The probability of being in a certain Bromage category at birth was similar in nulliparous and parous women in a general additive model adjusting for duration of epidural analgesia, number of rescue top-ups, and number of catheter manipulations (cumulative odds ratio: 1.18; 95% confidence interval: 0.98-1.41). Parous women required a higher time-weighted number and volume of rescue top-ups. CONCLUSIONS: The results of the randomised controlled trials on a reduced motor block with programmed intermittent epidural bolus seem generalisable to parturients typically not included in these trials.

Efficacy and safety of carbetocin given as an intravenous bolus compared with short infusion for Caesarean section - double-blind, double-dummy, randomized controlled non-inferiority trial.

BACKGROUND: Carbetocin is a synthetic oxytocin-analogue, which should be administered as bolus according to manufacturer's recommendations. A higher speed of oxytocin administration leads to increased cardiovascular side-effects. It is unclear whether carbetocin administration as short infusion has the same efficacy on uterine tone compared with bolus administration and whether haemodynamic parameters differ. METHODS: In this randomized, double-blind, non-inferiority trial, women undergoing planned or unplanned Caesarean section (CS) under regional anaesthesia received a bolus and a short infusion, only one of which contained carbetocin 100 mcg (double dummy). Obstetricians quantified uterine tone two, three, five and 10 min after cord-clamping by manual palpation using a linear analogue scale from 0 to 100. We evaluated whether the lower limit of the 95% CI of the difference in maximum uterine tone within the first five min after cord-clamping did not include the pre-specified non-inferiority limit of -10. RESULTS: Between December 2014 and November 2015, 69 patients were randomized to receive carbetocin as bolus and 71 to receive it as short infusion. Maximal uterine tone was 89 in the bolus and 88 in the short infusion group (mean difference -1.3, 95% CI -5.7 to 3.1). Bp, calculated blood loss, use of additional uterotonics, and side-effects were comparable. CONCLUSIONS: Administration of carbetocin as short infusion does not compromise uterine tone and has similar cardiovascular side-effects as a slow i.v. bolus. In accordance with current recommendations for oxytocin, carbetocin can safely be administered as short -infusion during planned or unplanned CS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02221531 and www.kofam.ch SNCTP000001197.

Long-term cognitive impairment after critical illness.

BACKGROUND: Survivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized. METHODS: We enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders. RESULTS: Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months. CONCLUSIONS: Patients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

Independent Component Analysis of Resting-State Functional Magnetic Resonance Imaging in Pedophiles.

INTRODUCTION: Neuroimaging and other studies have changed the common view that pedophilia is a result of childhood sexual abuse and instead is a neurologic phenomenon with prenatal origins. Previous research has identified differences in the structural connectivity of the brain in pedophilia. AIM: To identify analogous differences in functional connectivity. METHODS: Functional magnetic resonance images were recorded from three groups of participants while they were at rest: pedophilic men with a history of sexual offenses against children (n = 37) and two control groups: non-pedophilic men who committed non-sexual offenses (n = 28) and non-pedophilic men with no criminal history (n = 39). MAIN OUTCOME MEASURE: Functional magnetic resonance imaging data were subjected to independent component analysis to identify known functional networks of the brain, and groups were compared to identify differences in connectivity with those networks (or "components"). RESULTS: The pedophilic group demonstrated wide-ranging increases in functional connectivity with the default mode network compared with controls and regional differences (increases and decreases) with the frontoparietal network. Of these brain regions (total = 23), 20 have been identified by meta-analytic studies to respond to sexually relevant stimuli. Conversely, of the brain areas known to be those that respond to sexual stimuli, nearly all emerged in the present data as significantly different in pedophiles. CONCLUSION: This study confirms the presence of significant differences in the functional connectivity of the brain in pedophilia consistent with previously reported differences in structural connectivity. The connectivity differences detected here and elsewhere are opposite in direction from those associated with anti-sociality, arguing against anti-sociality and for pedophilia as the source of the neuroanatomic differences detected.

European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility.

It is 30 yr since the British Journal of Anaesthesia published the first consensus protocol for the laboratory diagnosis of malignant hyperthermia susceptibility from the European Malignant Hyperthermia Group. This has subsequently been used in more than 10 000 individuals worldwide to inform use of anaesthetic drugs in these patients with increased risk of developing malignant hyperthermia during general anaesthesia, representing an early and successful example of stratified medicine. In 2001, our group also published a guideline for the use of DNA-based screening of malignant hyperthermia susceptibility. We now present an updated and complete guideline for the diagnostic pathway for patients potentially at increased risk of developing malignant hyperthermia. We introduce the new guideline with a narrative commentary that describes its development, the changes to previously published protocols and guidelines, and new sections, including recommendations for patient referral criteria and clinical interpretation of laboratory findings.

[Management of postpartum hemorrhage (PPH): algorithm of the interdisciplinary D-A-CH consensus group PPH (Germany - Austria - Switzerland)]. / Management der postpartalen Blutung (PPH): Algorithmus der Interdisziplinären D-A-CH-Konsensusgruppe PPH (Deutschland - Österreich - Schweiz).

Postpartum hemorrhage (PPH) is one of the main causes of maternal deaths even in industrialized countries. It represents an emergency situation which necessitates a rapid decision and in particular an exact diagnosis and root cause analysis in order to initiate the correct therapeutic measures in an interdisciplinary cooperation. In addition to established guidelines, the benefits of standardized therapy algorithms have been demonstrated. A therapy algorithm for the obstetric emergency of postpartum hemorrhage in the German language is not yet available. The establishment of an international (Germany, Austria and Switzerland D-A-CH) "treatment algorithm for postpartum hemorrhage" was an interdisciplinary project based on the guidelines of the corresponding specialist societies (anesthesia and intensive care medicine and obstetrics) in the three countries as well as comparable international algorithms for therapy of PPH.The obstetrics and anesthesiology personnel must possess sufficient expertise for emergency situations despite lower case numbers. The rarity of occurrence for individual patients and the life-threatening situation necessitate a structured approach according to predetermined treatment algorithms. This can then be carried out according to the established algorithm. Furthermore, this algorithm presents the opportunity to train for emergency situations in an interdisciplinary team.

Is crystalloid co-loading necessary to prevent spinal hypotension during elective cesarean delivery? A randomized double-blind trial.

BACKGROUND: Hypotension is common during spinal anesthesia for cesarean delivery. Preventive strategies include fluid loading and phenylephrine. We hypothesized that if prophylactic phenylephrine infusion is used, omission of fluid loading would be non-inferior to fluid co-loading in maintaining cardiac output. We assumed that if there was a difference, the increase in cardiac output would be greater in the no-loading than in the co-loading group. METHODS: Term pregnant women scheduled for elective cesarean delivery were randomized to receive 1 L crystalloid co-loading or maintenance fluids only. Phenylephrine was titrated to maintain blood pressure. Changes in cardiac output following spinal anesthesia were the primary outcome. The study was powered as a non-inferiority trial, allowing the no-loading arm to have a 50% greater change in cardiac output. Heart rate, dose of phenylephrine, occurrence of nausea and vomiting, Apgar scores and neonatal acid base status were secondary outcomes. RESULTS: Data from 63 women were analyzed. In contrast to our hypothesis, there was 33% less increase in cardiac output with no loading (ratio 0.67, 95% CI 0.15 to 1.36), and 60% greater reduction of cardiac output with no loading (ratio 1.6, 95% CI 1.0 to 2.7). Total dose of phenylephrine was higher in the no-loading group. There may be a less favorable neonatal acid base status without volume loading. CONCLUSION: Omission of crystalloid co-loading leads to a decrease in cardiac output which has a potentially unfavorable impact on neonatal acid base status. We conclude that crystalloid co-loading may be useful in the presence of phenylephrine infusion.

[New aspects of obstetric anesthesia]. / Neues aus der geburtshilflichen Anästhesie.

BACKGROUND: The risk profile of patients in obstetric anesthesia has substantially changed. Even more so than other disciplines, obstetric anesthesia is therefore in the true sense of the word dependent on the close coordination of all concerned and a good interdisciplinary cooperation. AIM: This article explains the important anesthesiological risks connected with parturition and presents the corresponding concepts for prevention, diagnosis and management of peripartum complications. MATERIAL AND METHODS: The increase in the number of high risk pregnancies, which are mostly due to an increase in obesity, require clearly defined guidelines and interdisciplinary concepts which are described and discussed in this article. The neuraxial block is still the most effective procedure for treatment of birth pain and offers a promising new method with the programmed intermittent epidural boluses presented in this article. Finally, the German speaking countries Germany, Austria and Switzerland have developed a treatment algorithm for the management of postpartum hemorrhage which is presented here. RESULTS: The anesthesiological components of a risk pregnancy must be recognized early and include obesity, preeclampsia and drug-induced coagulopathy. Epidural analgesia is the most effective analgesic procedure in obstetrics. Patient-controlled remifentanil analgesia currently represents the best alternative in cases of contraindications for a neuraxial procedure. CONCLUSION: In risk situations, such as pre(eclempsia), emergency cesarean section, massive blood loss or other peripartum emergency situations, optimal interdisciplinary cooperation between midwives, obstetricians and anesthetists is required. However, not only emergency situations require a good interdisciplinary cooperation. Just as important is the cooperation to recognize risk pregnancies and a timely joint planning of the approaching birth.

The future of intensive care medicine.

Intensive care medical training, whether as a primary specialty or as secondary add-on training, should include key competences to ensure a uniform standard of care, and the number of intensive care physicians needs to increase to keep pace with the growing and anticipated need. The organisation of intensive care in multiple specialty or central units is heterogeneous and evolving, but appropriate early treatment and access to a trained intensivist should be assured at all times, and intensivists should play a pivotal role in ensuring communication and high-quality care across hospital departments. Structures now exist to support clinical research in intensive care medicine, which should become part of routine patient management. However, more translational research is urgently needed to identify areas that show clinical promise and to apply research principles to the real-life clinical setting. Likewise, electronic networks can be used to share expertise and support research. Individuals, physicians and policy makers need to allow for individual choices and priorities in the management of critically ill patients while remaining within the limits of economic reality. Professional scientific societies play a pivotal role in supporting the establishment of a defined minimum level of intensive health care and in ensuring standardised levels of training and patient care by promoting interaction between physicians and policy makers. The perception of intensive care medicine among the general public could be improved by concerted efforts to increase awareness of the services provided and of the successes achieved.

Final analysis and results of the Phase II SIMPLE dark matter search.

We report the final results of the Phase II SIMPLE measurements, comprising two run stages of 15 superheated droplet detectors each, with the second stage including an improved neutron shielding. The analyses include a refined signal analysis, and revised nucleation efficiency based on a reanalysis of previously reported monochromatic neutron irradiations. The combined results yield a contour minimum of σp=5.7×10(-3) pb at 35 GeV/c2 in the spin-dependent sector of weakly interacting massive particle (WIMP) proton interactions, the most restrictive to date for MW}≤60 GeV/c2 from a direct search experiment and overlapping, for the first time, with results previously obtained only indirectly. In the spin-independent sector, a minimum of 4.7×10(-6) pb at 35 GeV/c2 is achieved, with the exclusion contour challenging a significant part of the light mass WIMP region of current interest.

[Peripartum hemorrhage, diagnostics and treatment : Update of the S2k guidelines AWMF 015/063 from August 2022]. / Peripartale Blutungen, Diagnostik und Therapie : Update der S2k-Leitlinie AWMF 015/063 vom August 2022.

The current S2k guidelines on the diagnostics and treatment of peripartum hemorrhage are summarized in this article from the perspective of anesthesiology based on a fictitious case report. The update of the guidelines was written under the auspices of the German Society of Gynecology and Obstetrics with the participation of other professional societies and interest groups from Germany, Austria and Switzerland and published by the AWMF in 2022 under the register number 015/063.

Insulin-like growth factor-1 and delirium in critically ill mechanically ventilated patients: a preliminary investigation.

BACKGROUND: Delirium occurs frequently in the intensive care unit (ICU), but its pathophysiology is still unclear. Low levels of insulin-like growth factor 1 (IGF-1), a hormone with neuroprotective properties, have been associated with delirium in some non-ICU studies, but this relationship has not been examined in the ICU. We sought to test the hypothesis that low IGF-1 concentrations are associated with delirium during critical illness. METHODS: Mechanically ventilated medical ICU patients were prospectively enrolled, and blood was collected after enrollment for measurement of IGF-1 using radioimmunometric assay. Delirium and coma were identified daily using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale, respectively. The association between IGF-1 and delirium was evaluated with logistic regression. In addition, the association between IGF-1 and duration of normal mental state, measured as days alive without delirium or coma, was assessed using multiple linear regression. RESULTS: Among 110 patients, the median age was 65 years (IQR, 52-75) and APACHE II was 27 (IQR, 22 -32). IGF-1 levels were not a risk factor for delirium on the day after IGF-1 measurement (p = 0.97), at which time 65% of the assessable patients were delirious. No significant association was found between IGF-1 levels and duration of normal mental state (p = 0.23). CONCLUSIONS: This pilot study, the first to investigate IGF-1 and delirium in critically ill patients, found no association between IGF-1 and delirium. Future studies including serial measurements of IGF-1 and IGF-1 binding proteins are needed to determine whether this hormone has a role in delirium during critical illness.

First results of the Phase II SIMPLE dark matter search.

We report results of a 14.1 kg d measurement with 15 superheated droplet detectors of total active mass 0.208 kg, comprising the first stage of a 30 kg d Phase II experiment. In combination with the results of the neutron-spin sensitive XENON10 experiment, these results yield a limit of |a(p)|<0.32 for M(W)=50 GeV/c² on the spin-dependent sector of weakly interacting massive particle-nucleus interactions with a 50% reduction in the previously allowed region of the phase space, formerly defined by XENON, KIMS, and PICASSO. In the spin-independent sector, a limit of 2.3×10⁻5 pb at M(W)=45 GeV/c² is obtained.

Platypnea-orthodeoxia syndrome: an unusual cause of breathlessness in late pregnancy.

A pregnant patient with shortness of breath and arterial oxygen desaturation is presented. The primary and tentative initial diagnosis was pulmonary embolism. Her desaturation and dyspnea were aggravated in the upright compared with the supine position. The minimal response to supplemental oxygen suggested right-to-left shunting, which was confirmed by echocardiography. Shunting was minimal in the supine and maximal in the upright position, leading to the diagnosis of platypnea-orthodeoxia syndrome. By two weeks postpartum the patient's symptoms had resolved and shunting was undetectable.