Drug errors are a major safety issue during the peri-operative period. The prevalence of drug administration errors associated with the practice of neuraxial anaesthesia is not well known. Incorrect medication administered during neuraxial procedures may result in devastating consequences from both local vascular and neurological effects within the spinal canal as well as more distant effects due to the cephalad spread of the drug within the spinal canal. In addition, systemic effects following systemic reabsorption are a major concern following wrong drug injection via the intrathecal or epidural routes. Previously, we studied the nature of neuraxial drug errors in the obstetric population1 and also specifically to neuraxial tranexamic acid.2
Neuromuscular blocking drugs (NMBDs) are commonly stored and used along with other drugs in operating rooms. Generally, NMBDs do not cross the blood–brain barrier following intravenous administration. However, they may penetrate the central nervous system and cause neurotoxicity in the presence of a damaged blood-brain barrier. The inadvertent administration of NMBD during intrathecal or epidural anaesthesia provides an opportunity to learn about their neurological effects as well as their systemic effects by these routes of administration. This review is focused on summarising the clinical effects of neuraxial NMBDs and the human factors involved in the errors and will also suggest strategies to prevent such NMBD errors during neuraxial procedures.
We searched MEDLINE from 1 January 1965 to 31 May 2019 using the following terms ‘spinal anaesthesia’, ‘spinal anesthesia’, ‘spinal analgesia’, ‘epidural analgesia’, ‘epidural anaesthesia’, ‘epidural anesthesia’, ‘central neuraxial anaesthesia’, ‘central neuraxial anesthesia’ or ‘central neuraxial block’. All records were retrieved by a TIAB search (Title and Abstract). An additional search was performed using the terms ‘medication errors’ or ‘medical errors’. Articles containing any of the first search terms and any of the second search terms were retrieved. We included articles reporting errors involving NMBDs during central neuraxial anaesthesia or analgesia. We searched Google scholar using ‘related articles’ for all included articles. References from eligible articles were also manually searched to identify additional NMBD error reports. We excluded NMBD errors involving other routes and also errors related to other drugs whether by the neuraxial route or not.
A paper data collection form was used for individual NMBD error reports. This article record included details of the NMBD involved, dose administered, and the onset, duration and monitoring of neuromuscular effects. In addition, the clinical circumstances, consequences and their subsequent management were recorded. Duration of follow-up for individual patients was also noted. We used a Human Factors Analytical Classification System (HFACS), based on Reason's sliced Swiss cheese model, to analyse human factors.1,2 This well described model focuses on a systems approach and ascribes deficiencies or errors or failures to the holes in the cheese. The random holes in a Swiss cheese slice represent the potential for errors, but several slices represent defences, barriers or safeguards. HFACS1 (www.hfacs.com) describes 19 error categories in four layers of failure: Unsafe acts, preconditions for unsafe acts, unsafe supervision and organisational influences.
We qualitatively checked the reports for any or all our previously published four recommendations1 for eliminating errors: first, careful reading of the label on any drug ampoule or syringe before the drug is drawn up or injected; second, labelling all syringes; third, checking labels with a second person or a device (such as a barcode reader linked to a computer) before the drug is drawn up or administered; fourth, use of non-Luer lock connectors on all neuraxial equipment.
Twenty reports3–22 were identified involving seven NMBDs administered epidurally (14 cases)4–6,9,13–22 or intrathecally (6 cases).3,7,8,10–12 The drugs and doses administered, the clinical scenarios, neuromuscular manifestations, monitoring and management are summarised in Table 1 . All errors involving rocuronium,14–17 vecuronium,18–20 suxamethonium21,22 and cisatrcrium9 occurred via the epidural route only. Atracrium3–8 and pancuronium12,13 administration errors occurred via both the intrathecal and epidural routes. Fourteen patients received these neuraxial NMBDs while they were awake.3,5,7,8,10–16,19,21,22 The onset of action was delayed variably following epidural administration of rocuronium.14–17 Epidural administration of suxamethonium21,22 and vecuronium18–20 resulted in a prolonged duration of action.
Emergency airway interventions were required in five patients3,12,14,21,22 without any additional dose of intravenous NMBD. One adult9 and one paediatric patient17 required elective postoperative ventilation due to the error. Some of the clinical actions taken at the time included: consideration of the diagnosis of total spinal anaesthesia,14 repeat spinal anaesthesia,12 spontaneous recovery of partial neuromuscular blockade,3,7 avoiding the use of the epidural catheter after the incident,13 avoiding neuraxial anaesthesia during future surgery,3,16 administration of epidural normal saline5,13,18 alone or with steroids.9,17,21,22
Two patients who received intrathecal gallamine developed long lasting convulsions.10,11 Two patients reported a burning sensation during epidural rocuronium injections.14,15 No other neurological symptoms or toxicity were observed. Variable neurological follow-up was carried out from 1 h to up to 3 months.3–22
Human factors: Using the HFACS structure, failures were identified within each category.
These are classified as skill-based errors because they occurred during execution of a routine task.3–22 Perceptual errors occurred due to confusion or misjudgement by the assistant or the anaesthetist. Causes of errors included look-alike ampoules,7,11 same sized syringes5,9,13,21,22 and other reasons.4,6,15,16,18,20 Unlabelled syringes9,22 and failing to follow safety policies were considered violations.7,17
Preconditions for unsafe acts
Environmental factors including the similarity of ampoules and syringes were discussed in some reports.5,7,9,11,13,21,22 In one report,8 haste and distraction were mentioned as contributory factors. A three-way stopcock was used with one epidural catheter, which is not a routine practice.6
Inadequate supervision of individuals assisting with the neuraxial technique3,6,7,10,12 and delegation of tasks to an assistant that were outwith the assistant's scope of practice8 resulted in errors.
Variable practice of syringe labelling was reported including no use of labels,9,22 handwritten labels5 and use of a barcode.17 Lack of time was found in one error.8
Four measures are essential to prevent NMBD administration during neuraxial anaesthesia or analgesia.1,2 All of the suxamethonium21,22 and vecuronium,18–20 and majority of the rocuronium15–17 errors could have been prevented if the local anaesthetic drugs were prepared in non-Leur syringes. The simple measure of carefully reading the label on NMBD ampoules prior to drawing up the drug and rechecking the label on the syringe before injection could have prevented all atracrium,3–8 gallamine,10,11 pancuronium12,13 and rocuronium14–17 errors.
Our analysis provides some insight in predicting clinical consequences following the neuraxial administration of commonly used NMBDs. First, all groups of NMBDs are able to diffuse from the epidural space and cerebrospinal fluid (CSF) into the systemic circulation and have dose dependant neuromuscular junction (NMJ) effects (Table 1 ). Second, variable onset and duration of action is possible depending on the individual drug and clinical scenario. Third, NMJ monitoring to guide either spontaneous or drug assisted reversal and recovery of NMJ blockade was reliable. Finally, neurotoxicity, although a major worry, is unlikely following epidural administration.
Experimental studies have suggested that NMBDs interact with central neuronal nicotinic acetylcholine receptors or other ion channels to cause an increase in intracellular calcium ion concentrations leading to neuronal excitation and death.23–26 The clinical significance of these studies remain unclear. NMBDs can also act on muscarinic acetylcholine receptors in the brain.3,11,12,17
In the patients included in this review, neurotoxicity was not reported with the exception for Gallamine.10,11 The mechanisms of neurotoxicity related to gallamine are not fully explained. Delayed onset and migratory symptoms suggest cephalad travel of gallamine with CSF. Both patients who received gallamine intrathecally developed convulsions 90 min after administration which lasted for a long period.10,11 Another concern is the potential effects of NMBDs may have on spinal autonomic ganglia, which may cause haemodynamic disturbances.3 Laudanosine, a major metabolite of atracrium and cisatracrium, has potential to cause central nervous system side effects. However, its CSF levels are not known in errors reported. Two patients developed burning sensations during injection of rocuronium.14,15 This could be due to its direct effect on nerve roots, local changes due to osmolality, pH or excipients used for solution stability.
Due to their lower lipid solubility, higher molecular weight and reduced protein binding, NMBDs are expected to remain for a shorter time in the central nervous system when compared with local anaesthetics. Rocuronium was found to have variable onset of actions.14–17 This could be due to variable epidural anatomy, blood flow, co-administration of vasoconstrictor or unknown factors.
Vecuronium has a prolonged duration of action following epidural administration.18–20 This could be due to higher lipid solubility, which may lead to sequestration in the epidural fat. In addition, higher molecular weight of vecuronium may delay redistribution from the epidural space to plasma. If CSF concentration of NMBD is diluted with repeat spinal anaesthesia, onset of neuromuscular block (NMB) may be delayed.12
Due to lack of knowledge, neurology follow-up varied between hours to months (Table 1 ). Follow-up for 2 to 3 days appears reasonable as none of the patients was found to have any residual sequalae on the first postoperative day. We also suggest there is no need for cancellation of surgery. The protective or beneficial effects of epidural normal saline and/or steroid administration remain unknown.5,9,13,21,22 In all patients receiving NMBDs via any route, depth of NMJ blockade must be monitored. In our reported patients NMB was measured in the majority of cases using train of four ratio.
All are classified as skill-based errors.3–22 Many are also perceptual errors.4–7,9,11,13,15,16,20–22 How we perceive the objects during a task (e.g. drug preparation, administration or regional anaesthesia procedures) depends upon several factors including organisation and interpretation of our sensory impressions. In our analysis, incorrect visual perception of ampoules and syringes by the operator or assistant is evident in many reports.5,7–9,11,13,21,22 The reports do not elaborate on factors that might have led to perceptual errors. A frequently reported finding was the similar sizes and volumes in the syringes of NMBDs and local anaesthetics.5,13,21,22 Perception regarding syringe selection can be influenced by several factors. These include situational (e.g. task timing, neuraxial trolley design and setting, anaesthesia work station design and setting), individual (attitudes, biases, beliefs, communication, overconfidence, distraction, experiences, expectation, haste, inattention, knowledge, multitasking etc) and object for example ampoules and syringes (size, shapes, similarity, colour, labels, proximity, background location). When meaningful visual scanning is not performed carefully, or sensory information is not processed correctly identification of objects (syringes, ampoules or three-way taps in our analysed reports) may be compromised. Specific training, protocols and governance focusing on task awareness may help to minimise perceptual errors. For example, time management might have prevented one drug error by avoiding haste and distraction.8
HFACS is not commonly used when evaluating drug errors.1,2 There is little evidence in anaesthetic literature describing how human factors described in HFACS interact and culminate in failures when considering drug errors.27 One solution suggested is to utilise technology to minimise human factors. Despite technological measures such as availability of a barcode reader it was bypassed in one case.17 Social and professional trust placed on anaesthetic assistants could provide a source of error.5,7,8,11 Blind trust may prevent focus or oversight on the performance of other team members.
Specific preventive measures should be implemented to prevent serious morbidity or death from NMBDs drug administration errors.28–30 Manufacturing, procurement and pharmacy processes should be standardised to reduce errors. The responsibility of administering neuraxial drugs falls to the anaesthetist. Human factors involved in the task execution must be addressed.
The author previously published recommendations detailing measures to prevent neuraxial drug administration errors.1,2 These measures may also prevent NMBDs by other routes.
Carefully reading ampoule labels and labelled syringes is a fundamental step to avoiding drug errors. Implementing a double checking for high-risk medications is practical although difficult particularly during high turnover list and in private practice. It should be mandatory and professionals should embrace this change without delay. Alternatively, a handheld barcode scanner may be useful. This technology has been shown to reduce syringe swaps.31 Systems allowing labels to be printed and automatic recording of administration can be integrated into the software. Availability of barcode readers in low-income and middle-income countries could prove difficult due to financial constraints. Significantly, the majority of errors were reported from these countries. Barcode scanners rely on staff engagement for compliance. The effects on workflow and theatre efficiency would need to be studied before this measure was introduced into widespread clinical practice. Radiofrequency technology has also been reported for labelling syringes and vials.
Final recommendation is for the use of non Leur spinal or epidural needle and syringe systems. This would have prevented nearly 50% of errors. Recently, the International Organization for Standardization (ISO) standard published a standard (ISO 80369-6:2016 NRFit) to eliminate the possibility of cross connection between Leur and NRFit systems.32 NRFit systems are available, but their uptake is slow. This may be due to its, higher cost and doubt regarding its performance.
Syringe swap was the commonest clinical error in our analysis. Hew et al.33 reported 72% of epidural drug administration errors were due to syringe swaps. Syringe swap is a recognised drug error in the operating room.34 Proper labelling and location of prepared syringes may minimise syringe swaps. At present, there is no consensus among anaesthetists how best to implement and utilise these measures. The ASTM D 4774-94 and AS/NZS 4375 specify standards for size, font, background colour, nomenclature and adhesiveness.35 Numerous suggestions for clearly labelling have been made including along the axis of the barrel, circumferentially at the base (below the graduation markings) of barrel, double labels along the axis and circumferentially on the barrel, on both barrel and plunger, additional label to bridge the gap between syringe and needle/bung, black font with white background, group specific coloured labels. We use standard coloured labels for double labelling of the barrel. (along the axis and circumferentially) as it provides clear visibility whether syringe is in the hand for injection or is placed on the tray with whatever rotational orientation. This may also reduce the need to turn the syringe to turn for label checking and thereby reducing cognitive workload.
The debate surrounding colour coded labels continues.36 Fasting29 suggested that the use of different sized syringes is more important than colour coded labelling of syringes. In our analysis 5, 10 and 20 ml syringes were all involved in swap. For NMBDs dissimilar initial syllable of their names in bold capital letters of a larger size than would be used for the rest of the name printed in lower case letter has been suggested.37 Attaching ampoules or vials of NMBDs with the barrel or needle sheath/bung can improve tactile sensory input. Syringes with red coloured barrel or plunger are also available for NMBDs. Commercially prefilled colour labelled syringes seem an attractive alternative. However, storage and affordability are issues. Sterile labels in the spinal or epidural pack should be available so that left over local anaesthetic syringes do not remain unlabelled. Colour-coded tray may aid in identification and separation of high-risk medications used in anaesthesia practice.38
There are several limitations of this investigation. None of the reports measured epidural, CSF or plasma levels over time. Clinical features could not be always be identified because general anaesthesia was administered soon after error detection or already been established when error occurred. In some reported errors, local anaesthetics and/or opioids were given before, alongside or after administration of NMBDs. Use of intravenous NMBD occurred before or soon after the error. There are a limited number of reports that occurred in diverse clinical circumstances
In conclusion, NMBDs administration during neuraxial anaesthesia or analgesia result in dose dependant systemic neuromuscular blockade. Neuraxial NMBDs are likely to have delayed onset and prolonged duration of action following epidural administration. Commonly used NMBDs did not show clinical evidence of neurotoxicity. Prolonged neurological follow-up does not appear to be necessary. Neuraxial administration of NMBDs could be prevented by implementing the author's published recommendations. Further research is required to fully understand pharmacology of neuraxial NMBDs and application of HFACS to evaluate drug errors.
Acknowledgements relating to this article
Assistance with the study: Dr Nathan, Speciality trainee, Royal Oldham Hospital, Manchester for preparing raw tables and Dr Alastair Duncan, Consultant Anaesthetist, Manchester University NHS Foundation Trust for reviewing manuscript.
Financial support: none.
Conflicts of interest: none.
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