Discussion

Our analysis provides insight into systemic factors contributing to inadvertent KCl administration, illustrates clinical aspects and highlights important prevention points. We found many of the KCl errors occurred while managing acute pain (15 of 28 patients) following surgery in wards (eg, general, high dependency, or intensive care) via epidural catheter in situ or during management of chronic pain in procedure room (6 of 28 patients). We expected errors would be due to KCl infusion bag connected to epidural catheter. However, that was so for only 9 of 28 cases. In this series, neuraxial KCl resulted in serious morbidity in majority of patients, permanent disabilities in two patients, and death in three patients (one with undelivered baby). To our knowledge, apart from tranexamic acid,27 no other drug has caused more iatrogenic short-term and long-term morbidity as much as KCl in regional analgesia practice during perioperative period.

Only 2% (75–80 mmol) of total body (approximately 4000 mmol) potassium is extracellular. Following neuraxial KCl administration, decreased intracellular/extracellular potassium ratio reduces transneuronal membrane potential causing a partial or complete depolarization of the cell membrane.14 28 If high potassium level is persistent and profound, as in most cases in this series, it causes the inactivation of the voltage-gated sodium channels, making the axons refractory to excitation.28 29 Consequences of prolonged depolarization30 (eg, intracellular calcium accumulation) and hyperosmolarity-related adverse effects31 (eg, vascular damage) might have also played a role in damaging effects of KCl.

Wide range of concentrations (0.2%–15%) and doses (139–3000 mg) were administered either as a bolus or as an infusion via lumbar or thoracic epidural route (table 1 and online supplemental table). Earlier reports suggested concentrations less than 6.45%4 and dose less than 1500 mg11 are associated with complete recovery from neurological effects. However, these correlations about concentration and dose have been refuted in more recent reports as patients recovered completely despite receiving higher concentration10 11 13 23 and doses12 14 23 via epidural space. From our analyzed reports, which occurred in wide range of clinical scenarios, it is not possible to elucidate concentration–effect or dose–response relationship following neuraxial KCl administration. Several known and unknown intrinsic (eg, age, type of neurones, epidural and intrathecal anatomy and physiological factors, and level of injection) and extrinsic (eg, amount of KCl, physicochemical properties of the solution, bolus vs infusion, and presence of other drugs) factors may determine ultimate duration and completeness of recovery.

Another striking aspect of motor and sensory neurological consequences following neuraxial KCl is its similarity to clinical complications associated with neuraxial practice. This may lead to delay in suspicion and confirmation that KCl has been inadvertently administered. The inadequate block following intrathecal KCl was confused as a patchy block leading to readministration of KCl.22 Severe pain and paresthesia may be considered as a procedure-related trauma or as residual symptoms in chronic pain patients.8 Progressive motor and sensory block, in some cases associated with respiratory compromise, may simulate high or total spinal anesthesia 3 or back pain radiating to lower limb associated with motor and sensory block, and sphincter disturbance may lead to dilemma of epidural/spinal hematoma.11 Clinical features like sympathetic hyperactivity (tachycardia and hypertension), muscle spasms/clonic contractions, and diaphoresis may aid in suspecting KCl administration. The significance and correlation of the observed CSF hyperkalemia with patient clinical course remain unclear.1 3 7 21 MRI of the spine may not show any significant changes.6 19 22 24 Interestingly, in one patient,11 somatosensory evoked potentials (SSEP) recording led to suspicion of injection of the wrong substance and discovery of KCl vial.

Management of neuraxial KCl side effects is mainly symptomatic and supportive. Although steroid use was common, none of the reports quantified clinical neurological recovery benefit following intravenous and/or epidural steroid administration (table 2). It is difficult to demonstrate the benefits of epidural saline from our analysis because of large variation in KCl doses, presence of other drugs, different timings of administration relative to the incident and inconsistent volume (either bolus or infusion) administered, and so on (table 2). Authors who advocated its use suggest the beneficial effects of dilution of the drug with saline within epidural space, displacement of the drug from epidural to paravertebral space, and possibly increasing disposal via vascular route.32–34 However, NS flushing of epidural space following a large KCl amount administered in epidural space can result in further segmental spread of KCl with risks of quadriplegia, respiratory failure, and sympathetic hyperactivity.15 17 24 Therefore, its risk–benefits must be considered carefully.

For CSF lavage also, the optimal volume removal and ideal replacement fluid have not been well defined.22 Nevertheless, in the absence of other specific measures for intrathecal toxicity, early CSF lavage has a potential to reverse or limit the damage.1 22 In one patient,1 late (at least an hour) CSF lavage with peritoneal dialysis fluid decreased CSF potassium concentration from 27 to 2.2 mmol/L and was associated with unspecified early motor and sensory recovery. In another more recent case, Dias et al22 demonstrated regression of sensory block from T4 to T10 after CSF first lavage, which repeated after an hour. A pregnant woman (and her baby) died after receiving intrathecal 450 mg of potassium during elective lower segment caesarean section (LSCS). CSF lavage was not attempted in this case.

The incidences of perioperative medication errors are high, and there are many types of errors and contributing events.35 Many general and specific expert-based recommendations/opinions have been suggested involving organizational risk management policy (eg, lack of relevant medication policy) and safety culture, drug handling processes (eg, storage), pharmacy support, communication habits (eg, handover of care), workforce competency (eg, staff education and training), working environment, workstation structure, equipment design, use of technology, and so on. However, the relative importance of individual recommendation and its impact on prevention are limited by lack of high-quality, prospective medication safety studies.35 Neuraxial drug administration errors, although uncommon, are of high risk in nature, pose unique challenges, and require robust prevention strategies.27 36 37 Recently, Viscusi et al38 reviewed misconnection events involving either intravenous and/or neuraxial routes. They reported non-specific harm grading of only 5 KCl errors due to limited literature search. In contrast to their review, our analysis is comprehensive; includes all types of KCl errors; and details mechanism of errors, clinical circumstances (eg, perioperative phase), clinical sequelae, management options, human factors, and safety measures to prevent.

Between 1999 and 2002, safety organizations in the USA, the UK, and Canada issued safety alerts following fatal intravenous administration errors of KCl.39 The contributory factors identified were availability and storage of concentrated potassium ampoules/vials and unstandardized KCl solutions in the wards.40 Fatigue, night shift, hurry, multitasking, and inattention may cause incorrect visual perception of ampoules or vials or syringes or infusion bags or lines or pumps. For 19 of 28 patients in this series, irrespective of clinical location, prevention would depend on clinician and computer (eg, barcoding) or two clinicians checking labels both when the drugs are drawn up and immediately before injection. For only 9 of 25 cases, intravenous–epidural line confusion led to misconnections in this series. Therefore, our findings are limited by low level of evidence based on analysis of small number of reports. NRFit could prevent at most half the KCl incidents (upper confidence limit of 48%).

In conclusion, although rare, KCl administration errors via epidural or intrathecal route can be devastating. KCl drug administration errors predominantly occurred in wards in the postoperative period. Its clinical neurological adverse effects may be confused with other neuraxial complications. Connector technological devices are unlikely to prevent all errors as only few were due to intravenous–epidural catheter misconnections. To prevent neuraxial drug errors, human or technology use for double checking is required.