Daniel W. Wheeler

Medication errors in anaesthesia and critical care

There is an increasing recognition that medication errors are causing a substantial global public health problem, as many result in harm to patients and increased costs to health providers. However, study of medication error is hampered by difficulty with definitions, research methods and study populations. Few doctors are as involved in the process of prescribing, selecting, preparing and giving drugs as anaesthetists, whether their practice is based in the operating theatre, critical care or pain management. Anaesthesia is now safe and routine, yet anaesthetists are not immune from making medication errors and the consequences of their mistakes may be more serious than those of doctors in other specialties. Steps are being taken to determine the extent of the problem of medication error in anaesthesia. New technology, theories of human error and lessons learnt from the nuclear, petrochemical and aviation industries are being used to tackle the problem.

Calculation of doses of drugs in solution: Are medical students confused by different means of expressing drug concentrations?

AbstractIntroduction: Our hypothesis was that clinical medical students find the different means of expressing the concentration of drugs in solution confusing. We are concerned that lack of formal teaching on this topic may make students liable to make drug dosing errors after they have qualified. Administering the wrong volume of a drug may have serious consequences for patient safety. Study design and participant group: Web-based electronic multiple-choice examination of clinical medical students. Methods: We asked clinical medical students at our university three multiple-choice questions concerning the concentration of lidocaine (lignocaine) and epinephrine (adrenaline) in solution and the maximal recommended dose of lidocaine. The incorrect options were wrong by factors of between 4 and 1000. Results: One hundred and sixty-eight clinical students out of 350 contacted responded to an invitation to participate (response rate 48%). Twenty-seven percent answered every question incorrectly and 10% answered all three correctly. The mean score for all students was only 1.24 out of 3 (standard error 0.96). However, final-year students performed significantly better (p = 0.016), implying that some knowledge had been acquired informally. Their higher mean score resulted from correctly identifying the amount of epinephrine (p = 0.005) and lidocaine (p = 0.018) more frequently. Only 27% knew the maximal recommended dose of lidocaine, with no difference between years (p = 0.724). Conclusions: A substantial majority of medical students are unable to calculate the mass of a drug in solution correctly. There is evidence that some students are picking up this skill during the course, because final-year students performed significantly better than first-year students. Modern medical student pharmacology teaching is highly sophisticated, encompassing genomics, molecular and cell biology. The ability to calculate drug doses safely appears to have been overlooked. Students should be familiar with these concepts, so as to avoid dose errors and associated morbidity, mortality and cost when they begin prescribing. To simplify calculations, drug packaging should express the concentration of drugs in solution solely as mass per unit volume, e.g. milligrams per millilitre.

Errors during the preparation of drug infusions: a randomized controlled trial

BACKGROUND We investigated the extent and frequency of dose errors and treatment delays made as a consequence of preparing drug infusions at the bedside, rather than using pre-filled syringes. METHODS Forty-eight nurses with critical care experience volunteered to take part in this randomized, blinded, controlled study conducted in the simulation centre of an urban hospital. They assisted in the management of a simulated patient with septic shock. Vasopressor infusions were prepared either by diluting concentrated drugs from ampoules or were provided in syringes pre-filled beforehand by an intensive care unit resident. RESULTS The time taken for the infusion to be started and the final concentration of the drugs were measured. We also measured the concentration of infusions prepared by a pharmacist and a pharmaceutical company. Nurses took 156 s to start infusions when using pre-filled syringes compared with 276 s when preparing them de novo, a mean delay of 106 s [95% confidence interval (CI) 73-140 s, P<0.0001]. One infusion prepared from ampoules contained one-fifth of the expected concentration of epinephrine; another contained none at all. Medication errors were 17.0 times less likely when pre-filled syringes were used (95% CI 5.2-55.5), and infusions prepared by pharmacy and industry were significantly more likely to contain the expected concentration (P<0.001 for norepinephrine and P=0.001 for epinephrine). CONCLUSIONS Providing drug infusions in syringes pre-filled by pharmacists or pharmaceutical companies would reduce medication errors and treatment delays, and improve patient safety. However, this approach would have substantial financial implications for healthcare providers, especially in less developed countries.

Anaesthetic Impairment of Immune Function Is Mediated via GABA A Receptors

Background GABAA receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs [1]. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear [2]. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die [3]–[6]. As many anaesthetics act via GABAA receptors [7], the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. Principal Findings We demonstrate, using RT-PCR, that monocytes express GABAA receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABAA receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABAA receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. Significance Our results show that functional GABAA receptors are present on monocytes with properties similar to CNS GABAA receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABAA receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABAA receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.

Factors influencing doctors’ ability to calculate drug doses correctly

Doctors and medical students are more likely to make errors in drug dose calculations when the strengths of drug solutions are expressed as ratios or percentages. We have already described how a doctors specialty influences their drug dose calculation skills, having surveyed almost 3000 doctors in an online survey. Better teaching of drug administration skills or reinforcement of existing skills would appear to be needed. We sought to identify doctors that might benefit particularly from such teaching by other means than specialty alone, by subjecting existing data to further analysis. Almost 3000 doctors subscribing to a UK‐based internet content provider had participated in an online questionnaire concerning drug‐dose calculation. Each doctors score in the multiple choice questionnaire was cross referenced with demographic data obtained from the hosts of the original survey whilst maintaining anonymity. Newly and recently qualified doctors, and doctors working in the community, struggled most with the calculations (p < 0.0001). There were also highly significant differences in the performances of doctors from different medical schools (p < 0.0001). As a new training programme for junior doctors is being introduced in the UK; we recommend that drug administration skills are given a prominent place in the curriculum, and again call for the standardisation of ampoule labelling to mass concentration.

Synthetic self-assembling clostridial chimera for modulation of sensory functions.

Clostridial neurotoxins reversibly block neuronal communication for weeks and months. While these proteolytic neurotoxins hold great promise for clinical applications and the investigation of brain function, their paralytic activity at neuromuscular junctions is a stumbling block. To redirect the clostridial activity to neuronal populations other than motor neurons, we used a new self-assembling method to combine the botulinum type A protease with the tetanus binding domain, which natively targets central neurons. The two parts were produced separately and then assembled in a site-specific way using a newly introduced ‘protein stapling’ technology. Atomic force microscopy imaging revealed dumbbell shaped particles which measure ∼23 nm. The stapled chimera inhibited mechanical hypersensitivity in a rat model of inflammatory pain without causing either flaccid or spastic paralysis. Moreover, the synthetic clostridial molecule was able to block neuronal activity in a defined area of visual cortex. Overall, we provide the first evidence that the protein stapling technology allows assembly of distinct proteins yielding new biomedical properties.

Integrated approaches to academic anaesthesia – the Cambridge experience

There is mounting concern about the pressures experienced by University Departments of Anaesthesia, which, if lost, could threaten undergraduate peri‐operative medicine teaching, development of critical appraisal skills among anaesthetists, and the future of coherent research programs. We have addressed these problems by establishing a foundation course in scientific methods and research techniques (the Cambridge SMART Course), complemented by competitive, fully funded, 12‐month academic trainee attachments. Research conducted during academic attachments has been published and used to underpin substantive grant applications allowing work towards higher degrees. Following the attachment, a flexible scheme ensures safe reintroduction to clinical training. Research at consultant level is facilitated by encouraging applications for Clinician Scientist Fellowships, and by ensuring that the University Department champions, legitimises and validates the allocation of research time within the new consultant contract. We believe that these are important steps in safeguarding research and teaching in anaesthesia, critical care and peri‐operative medicine.

Case Report: Neuropathic pain in a patient with congenital insensitivity to pain

We report a unique case of a woman with Channelopathy-associated Insensitivity to Pain (CIP) Syndrome, who developed features of neuropathic pain after sustaining pelvic fractures and an epidural hematoma that impinged on the right fifth lumbar (L5) nerve root. Her pelvic injuries were sustained during painless labor, which culminated in a Cesarean section. She had been diagnosed with CIP as child, which was later confirmed when she was found to have null mutations of the SCN9A gene that encodes the voltage-gated sodium channel Nav1.7. She now complains of troubling continuous buzzing in both legs and a vice-like squeezing in the pelvis on walking. Quantitative sensory testing showed that sensory thresholds to mechanical stimulation of the dorsum of both feet had increased more than 10-fold on both sides compared with tests performed before her pregnancy. These findings fulfill the diagnostic criteria for neuropathic pain. Notably, she mostly only experiences the negative symptoms (such as numbness and tingling, but also electric shocks), and she has not reported sharp or burning sensations, although the value of verbal descriptors is somewhat limited in a person who has never felt pain before. However, her case strongly suggests that at least some of the symptoms of neuropathic pain can persist despite the absence of the Nav1.7 channel. Pain is a subjective experience and this case sheds light on the transmission of neuropathic pain in humans that cannot be learned from knockout mice.

Pulling the plug on ad hoc critical incident training

Safe airway management and ventilation is one of the central tenets of anaesthesia. Fortunately, the failure of equipment for gas delivery is a rare event. An analysis of the database of the American Society of Anesthesiologists Closed Claims Project between 1962 and 1991 found that gas delivery equipment was associated with only 2% (72) of these claims, but the consequences tended to be grave: three-quarters involved death or permanent brain damage. In a recent simulation-based study, the only error made by all participants related to the management of a failure in oxygen supply. It is clear that anaesthetists should be trained to recognize and deal with problems of this type, and reinforce those skills regularly throughout their careers. But what is the best way of doing this? Recently, an experienced and highly regarded consultant anaesthetist faced disciplinary action for carrying out a training exercise in which he told a trainee with whom he was working that he was leaving the operating theatre for a coffee break, switched off the mains electricity supply to the anaesthetic machine without checking that the backup battery was functioning and left the trainee to deal with the consequences. Neither the trainee nor the patient had been informed that he intended to conduct such a training procedure. The ‘Fitness to Practice Panel’ of the General Medical Council found that in doing this he had exposed the patient to a risk of harm (although no harm resulted as the trainee successfully initiated alternative means of ventilation). The panel concluded that the consultant’s actions were out of character and misguided, but did not constitute misconduct. In view of his exemplary character, it was determined that his fitness to practice was not impaired, and no further action was taken. The case was widely reported in the media, and many anaesthetists commented at the time that they too had been tested in similar ways during their training. Expectations within society change over the course of a career. When one of us began practising anaesthesia in the early 1980s, this story would have been unremarkable. That is no longer the case, and it is easy to imagine how it would be regarded by the general public today. Many patients may accept the value of such training, but the keys are consent and transparency. The trainer should explain to the patient beforehand that he or she would like to conduct some safety drills during the case to ensure that the operating theatre team can manage real emergencies effectively. It should be made clear that these drills will be supervised and are unlikely to lead to harm, and that declining consent would not affect the patient’s treatment. It would be prudent for consent to be recorded in the notes. Many patients may decline, but this is their right. More pragmatically, it is also a price worth paying when the alternative may lead to disciplinary action and adverse publicity. Furthermore, there is, today, another way of achieving the same educational objectives. It is no longer necessary to expose people to risk to teach physicians how to manage scenarios that are rare but may have serious consequences for patients. Such incidents can easily be reproduced in a high-fidelity patient simulator without involving patients at all. Modern simulators driven by sophisticated physiological and pharmacological models allow properly structured exercises with defined educational objectives and assessment criteria to be undertaken with very high levels of realism. Participants typically engage strongly in the simulated scenarios and find the experience convincing and of value. Training may focus on the routine (teaching a foundation year trainee how to deal with a patient with arrhythmia) or the exotic (such as managing malignant hyperpyrexia). Technical and non-technical skills can be honed. Opportunities for facilitated reflection can be provided immediately afterwards, without the need to attend to the next clinical priority. Anaesthesia Resource Crisis Management (ACRM) courses are now well established in many centres. For example, in the Effective Management of Anaesthesia Crisis (EMAC) courses run under licence

Factors affecting the concentration of electrolyte infusions prepared from stock solutions.

Background Wide variation in the concentrations of electrolyte infusions prepared from stock solutions has previously been reported. Layering of viscous stock electrolyte solutions in their diluent can lead to high concentrations being delivered during the infusion, resulting in potentially very serious medication errors which have caused deaths. Objective To determine the safest way of preparing homogenous electrolyte solutions for parenteral infusion. Methods The study examined how the concentration of potassium and magnesium varied during infusions after concentrated stock solutions had been diluted to 400 mmol/l with 0.9% sodium chloride. It also examined the use of syringes compared to polyvinyl chloride (PVC) bags, agitating vigorously with a ‘vortex’ mixer compared to inversion, and the influence of allowing the infusions to stand for 24 h before administration. The study was conducted in November 2009. Results It was found that, in general, the concentrations of potassium and magnesium solutions are less variable if they are prepared in PVC bags rather than syringes. Vigorous mixing of concentrated stock solutions with diluent and allowing preparations to stand for 24 h also improved the homogeneity of the infusions. However, even with meticulous preparation, some infusions deviated from the expected concentration by more than 10%. Conclusion It is recommended that electrolyte infusions are prepared and provided by the pharmaceutical industry in prefilled syringes or bags. Given the likely cost of these products, an alternative would be to prepare infusions in pharmacy in advance, using PVC bags rather than syringes, and that they should be agitated vigorously with a ‘vortex’ mixer.