Intravenous drug dose optimization and drug effect monitoring in anaesthesia

Dit proefschrift onderstreept het belang van het optimaliseren van de dosering van anesthetica en geeft een beschrijving van de middelen die de anesthesiologen hebben om dit doel te bereiken. Twee belangrijke onderwerpen komen hierbij aan bod. Ten eerste hebben we onderzocht wat de invloed is van hersentumoren in de frontale hersenkwab op de pharmacokinetiek (de manier waarop het lichaam medicatie verwerkt) en pharmacodynamiek (de invloed van medicatie op het lichaam) van propofol bij patiënten die hieraan geopereerd werden. Op basis van ons onderzoek concluderen wij dat hersentumoren wel invloed hebben op de farmacokinetiek, maar niet op de farmacodynamiek van propofol. Ten tweede hebben we beoordeeld hoe effectief verschillende hypnose en analgesie monitors (BIS, CVI, CI, CS) zijn als hulpmiddel bij het optimaliseren van een anesthetische dosis in de algemene populatie. Uiteindelijk concluderen wij dat de huidige generatie hypnose en analgesie monitors anesthesiologen wel beter in staat stellen om de medicatie dosis te optimaliseren dan de huidige praktijk (standaard dosering schema’s en doseren op geleide van hemodynamische variabelen), maar dat ze nog steeds belangrijke tekortkomingen hebben

Clinical pharmacokinetics and pharmacodynamics of propofol

Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter -aminobutyric acid (GABA) at the GABA(A) receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Due to its narrow therapeutic margin, propofol should only be administered by practitioners trained and experienced in providing general anaesthesia. Many pharmacokinetic (PK) and pharmacodynamic (PD) models for propofol exist. Some are used to inform drug dosing guidelines, and some are also implemented in so-called target-controlled infusion devices, to calculate the infusion rates required for user-defined target plasma or effect-site concentrations. Most of the models were designed for use in a specific and well-defined patient category. However, models applicable in a more general population have recently been developed and published. The most recent example is the general purpose propofol model developed by Eleveld and colleagues. Retrospective predictive performance evaluations show that this model performs as well as, or even better than, PK models developed for specific populations, such as adults, children or the obese; however, prospective evaluation of the model is still required. Propofol undergoes extensive PK and PD interactions with both other hypnotic drugs and opioids. PD interactions are the most clinically significant, and, with other hypnotics, tend to be additive, whereas interactions with opioids tend to be highly synergistic. Response surface modelling provides a tool to gain understanding and explore these complex interactions. Visual displays illustrating the effect of these interactions in real time can aid clinicians in optimal drug dosing while minimizing adverse effects. In this review, we provide an overview of the PK and PD of propofol in order to refresh readers' knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made

Intraoperative monitoring of the central and peripheral nervous systems:a narrative review

The central and peripheral nervous systems are the primary target organs during anaesthesia. At the time of the inception of the British Journal of Anaesthesia, monitoring of the central nervous system comprised clinical observation, which provided only limited information. During the 100 yr since then, and particularly in the past few decades, significant progress has been made, providing anaesthetists with tools to obtain real-time assessments of cerebral neurophysiology during surgical procedures. In this narrative review article, we discuss the rationale and uses of electroencephalography, evoked potentials, near-infrared spectroscopy, and transcranial Doppler ultrasonography for intraoperative monitoring of the central and peripheral nervous systems.</p

Surviving the storm:manual vs. mechanical chest compressions onboard a lifeboat during bad weather conditions

Objective: It is challenging for rescuers to perform cardiopulmonary resuscitation (CPR) onboard lifeboats, particularly during rough weather. A mechanical chest compression device (MCD) may provide better quality chest compressions. The aim of this study was to compare the quality of chest compressions performed by lifeboat-crewmembers with those of a MCD during rough-sea conditions.Methods: Lifeboat-crewmembers were scheduled to provide compression-onlyCPR on a resuscitation-mannequin during two sets of five 6-min epochs on alifeboat at sea in two different weather-conditions. Simultaneously a MCD wasused for compression-only CPR on another mannequin onboard the lifeboat. Ona third occasion compressions by MCD only were measured due to COVID-19restrictions. The primary outcome variable was the quality of chest compression,evaluated using published variables and standards (mean compression depthand compression frequency, percentage correct compression depth, percentageof not leaning on the thorax, percentage of correct hand placement on thethorax, hands-off-time).Results: Six male lifeboat-crewmembers (mean age 35 years) performed CPRduring two different weather conditions. In weather-conditions one (wind∼6–7 Beaufort/wave-height: 100–150 cm) quality of manual compressions wassignificantly worse than mechanical compressions for mean compression depth(p &lt; 0.05) and compression frequency (p &lt; 0.05), percentage correct compression depth (p &lt; 0.05), percentage of not leaning on the thorax (p &lt; 0.05), and hands off time (p &lt; 0.05). Crewmembers could only perform CPR for a limited time-period (sea-conditions/seasickness) and after one set of five epochs measurements were halted. In weather-condition two (wind ∼9 Beaufort/wave-height ∼200 cm) similar results were found during two epochs, after which measurements were halted (sea-conditions/seasickness). In weather-condition three (wind ∼7 Beaufort/wave-height ∼300–400 cm) MCD compressions were according to resuscitation-guidelines except for three epochs during which the MCD was displaced.Conclusion: Crewmembers were only able to perform chest-compressions for alimited time because of the weather-conditions. The MCD was able to providegood quality chest compressions during all but three epochs during the studyperiod. More research is needed to determine whether MCD-use in real-lifecircumstances improves outcome. Inclusion of data on use of a MCD on lifeboatsshould be considered in future revisions of the USFD and resuscitation guidelines

Anesthesia and intraoperative neurophysiological spinal cord monitoring

Purpose of review We will explain the basic principles of intraoperative neurophysiological monitoring (IONM) during spinal surgery. Thereafter we highlight the significant impact that general anesthesia can have on the efficacy of the IONM and provide an overview of the essential pharmacological and physiological factors that need to be optimized to enable IONM. Lastly, we stress the importance of teamwork between the anesthesiologist, the neurophysiologist, and the surgeon to improve clinical outcome after spinal surgery. Recent findings In recent years, the use of IONM has increased significantly. It has developed into a mature discipline, enabling neurosurgical procedures of ever-increasing complexity. It is thus of growing importance for the anesthesiologist to appreciate the interplay between IONM and anesthesia and to build up experience working in a team with the neurosurgeon and the neurophysiologist. Safety measures, cooperation, careful choice of drugs, titration of drugs, and maintenance of physiological homeostasis are essential for effective IONM

What is new in microcirculation and tissue oxygenation monitoring?

Ensuring and maintaining adequate tissue oxygenation at the microcirculatory level might be considered the holy grail of optimal hemodynamic patient management. However, in clinical practice we usually focus on macro-hemodynamic variables such as blood pressure, heart rate, and sometimes cardiac output. Other macro-hemodynamic variables like pulse pressure or stroke volume variation are additionally used as markers of fluid responsiveness. In recent years, an increasing number of technological devices assessing tissue oxygenation or microcirculatory blood flow have been developed and validated, and some of them have already been incorporated into clinical practice. In this review, we will summarize recent research findings on this topic as published in the last 2 years in the Journal of Clinical Monitoring and Computing (JCMC). While some techniques are already currently used as routine monitoring (e.g. cerebral oxygenation using near-infrared spectroscopy (NIRS)), others still have to find their way into clinical practice. Therefore, further research is needed, particularly regarding outcome measures and cost-effectiveness, since introducing new technology is always expensive and should be balanced by downstream savings. The JCMC is glad to provide a platform for such research

Performance of Basic Life Support by Lifeboat Crewmembers While Wearing a Survival Suit and Life Vest:A Randomized Controlled Trial

Introduction: Crewmembers of the “Royal Netherlands Sea Rescue Institution” (KNRM) lifeboats must wear heavy survival suits with integrated lifejackets. This and the challenging environment onboard (boat movements, limited space) might influence Basic Life Support (BLS) performance. The primary objective of this study was to assess the impact of the protective gear on single-rescuer BLS-quality. Material and Methods: Sixty-five active KNRM crewmembers who had recently undergone a BLS-refresher course were randomized to wear either their protective gear (n = 32) or their civilian clothes (n = 33; control group) and performed five 2-min sessions of single rescuer BLS on a mannequin on dry land. BLS-quality was assessed according to Dutch and European Resuscitation guidelines. A between group analysis (Mann-Whitney U) and a repeated within group analysis of both groups (Friedman test) were performed. Results: There were no major demographic differences between the groups. The protective gear did not significant impair BLS-quality. It was also not associated with a significant increase in the perceived exertion of BLS (Borg's Rating scale). Compression depth, compression frequency, the percentage of correct compression depth and of not leaning on the thorax, and ventilation volumes in both groups were suboptimal when evaluated according to the BLS-guidelines. Conclusions: The protective gear worn by KNRM lifeboat-crewmembers does not have a significant influence on BLS-quality under controlled study conditions. The impact and significance on outcome in real life situations needs to be studied further. This study provides valuable input for optimizing the BLS-skills of lifeboat crewmembers