Encephalopathy after Erector Spinae Plane Block When Should LAST Be First?

Alejandro Chapa-Rodriguez²*^ORCID,Nirajan Kandel^1ORCID, Hillary Starling⁴, Gabriela Domínguez Arocho³, Yasier Medina⁵, Ryan Huttinger⁴, Satyanarayana Vaidy^2ORCID

¹Department of Internal Medicine, Cape Fear Valley Medical Center, Fayetteville, North Carolina, USA

²Department of Pulmonary and Critical Care Medicine, Cape Fear Valley Medical Center, Fayetteville, North Carolina, USA

³Department of Pharmacy, Cape Fear Valley Medical Center, Fayetteville, North Carolina, USA

⁴Department of Cardiothoracic Surgery, Cape Fear Valley Medical Center, Fayetteville, North Carolina, USA

⁵Department of Neurology, Cape Fear Valley Medical Center, Fayetteville, North Carolina, USA

^*Corresponding Author: Alejandro Chapa-Rodriguez, Department of Pulmonary and Critical Care Medicine

Cape Fear Valley Medical Center Fayetteville, North Carolina, USA.

Received: 18 August 2026; Accepted: 24 August 2026; Published: XX- September 2026

Introduction

Postoperative encephalopathy in the intensive care unit carries a broad differential, with delirium, residual sedation, stroke, and metabolic derangements typically considered first (1). LAST is a rare but potentially fatal complication of regional anesthesia that classically presents with CNS excitation followed by cardiovascular collapse (2,6). Atypical, delayed, and CNS-only presentations are increasingly recognized and can mimic postoperative delirium or emergence phenomena, delaying recognition and treatment (1-3). ESP blocks have gained popularity for thoracic surgery analgesia but require deposition of large local anesthetic volumes into a highly vascular fascial plane, producing peak plasma concentrations comparable to intercostal blocks and a recognized LAST risk (4,5). This case illustrates a rare presentation of LAST as isolated encephalopathy with hallucinations and frames it within the published epidemiology of LAST presentations to argue for broader clinical suspicion.

Case Presentation

A 70-year-old man weighing 99.7kg with past medical history of essential hypertension, type 2 diabetes mellitus, chronic obstructive pulmonary disease, prior stroke, and prostate cancer in remission. Admitted for spontaneous pneumothorax from a ruptured bleb with a new left upper lobe nodule. He underwent robotic-assisted thoracoscopic wedge resection, pleurodesis, and lymph node sampling under general anesthesia. He received a preoperative bupivacaine ESP block with 20 mL of liposomal bupivacaine (Exparel) and 10 mL of 0.5% bupivacaine for postoperative analgesia. The immediate postoperative period was unremarkable. Approximately four hours postoperatively the patient developed visual hallucinations that progressed over the following four hours to profound encephalopathy with markedly depressed consciousness, eye opening only to noxious stimuli and no verbal response.

Investigations

Examination showed no rigidity, clones, or fever. Deep tendon reflexes were absent, with flexor plantar responses bilaterally. Non-contrast computed tomography (CT) of the head and CT angiography of the head and neck showed no acute cerebrovascular abnormalities, making a major acute cerebrovascular event less likely.  Bedside point-of-care blood glucose, arterial blood gas, chest radiograph, complete blood count, and comprehensive metabolic panel were all unremarkable. There was no response to a trial of flumazenil or naloxone.

Differential Diagnosis

The principal differentials considered included postoperative delirium, residual sedation or emergence phenomenon, acute ischemic stroke or other cerebrovascular events, metabolic encephalopathy, nonconvulsive status epilepticus, and LAST. CT and CT angiography showed no acute cerebrovascular abnormality, while metabolic studies did not identify hypoglycemia, hypercapnia, hyponatremia, or other common metabolic derangements. Absence of response to flumazenil and naloxone reduced the likelihood of residual benzodiazepine or opioid effect. Although nonconvulsive seizure activity and a small acute ischemic lesion could not be definitively excluded without EEG or diffusion-weighted MRI, the patient’s rapidly deteriorating mental status and concern for time-sensitive LAST prompted treatment without delaying for further diagnostic testing. The temporal relationship to the bupivacaine ESP block, together with the otherwise unrevealing evaluation, brought LAST to the forefront of the differential diagnosis.

Treatment

Given the recent ESP block with bupivacaine and the systematic exclusion of alternative diagnoses, empirical 20% intravenous lipid emulsion was administered. The patient initially received a 100 mL bolus, after which his mental status improved from profound encephalopathy to intermittent eye opening with persistent confusion. Because neurological recovery remained incomplete, a repeat bolus was administered, followed by continued lipid emulsion infusion. In total, approximately 300 mL was administered by infusion over an estimated 45 minutes. Following repeat dosing, the patient continued to improve without recurrent neurological or cardiovascular deterioration.

Outcome and Follow-up

Mental status improved promptly after initiation of lipid emulsion therapy, with complete neurological recovery within 24 hours. There were no recurrent neurological or cardiovascular events during the remainder of the hospitalization. The patient was discharged with no neurological sequelae.

Discussion

LAST is a recognized but uncommon complication of regional anesthesia, with a contemporary incidence of approximately 1 per 1000 applications (1,7). The rising use of fascial plane blocks, ambulatory catheter infusions, and office-based local anesthetic administration has expanded the population at risk (1,8). ESP blocks in particular produce peak plasma concentrations 30 to 60 minutes after injection and sustained systemic exposure thereafter (4,5); symptom onset four hours post-block, as in our patient, is biologically consistent with this profile.

The clinical spectrum of LAST is broader than the textbook description suggests, and major society guidelines have explicitly broadened the diagnostic criteria (Table 1). The ASRA 2018 Practice Advisory and 2020 Checklist, the Association of Anesthetists 2023 Quick Reference Handbook, and the Japanese Society of Anesthesiologists 2019 Practical Guide each recognize isolated CNS findings, isolated cardiovascular findings, or delayed onset as valid LAST presentations (5,6,10,11). Vasques and colleagues analyzed 67 LAST events between 2010 and 2014: isolated CNS toxicity accounted for 50%, combined CNS and cardiovascular toxicity for 36%, and isolated cardiovascular toxicity for 14% (7). Seizure was the most common single feature at 54%, but prodromal symptoms including hallucinations, confusion, slurred speech, tinnitus, and tremor, accounted for 40% of CNS manifestations, more than doubling from 18% in the previous three decades (7,9). The Macfarlane review documented isolated CNS effects in 32% of cases; approximately 53% of manifestations occurred within 10 minutes, 19% between 11 minutes and 1 hour, and 8% after 12 hours (1).

Table 1: Comparison of major society guidelines for LAST recognition and management.

Reference numbers in column two correspond to the reference list. ASRA = American Society of Regional Anesthesia and Pain Medicine; AAGBI = Association of Anesthetists; JSA = Japanese Society of Anesthesiologists; AHA = American Heart Association; ACLS = Advanced Cardiac Life Support; ILE = intravenous lipid emulsion; ABC = airway, breathing, circulation; LA = local anesthetic.

Despite this guideline convergence, most clinicians anchor on the classic teaching: seizures progressing to hemodynamic collapse. In practice the threshold for invoking LAST often becomes the simultaneous presence of CNS and cardiovascular instability, a combination that occurs in a minority of published cases. To contextualize our case, we performed a focused PubMed search across "lidocaine", "bupivacaine", "liposomal bupivacaine", "ropivacaine", and "local anesthetic" associated with systemic toxicity terms. The search identified 81 records, after removal of 35 duplicates, 46 unique publications were assessed for eligibility. Twenty-eight were excluded, leaving 18 publications reporting 21 LAST cases for inclusion in Table 2 (12-29). Of the 21 cases, 11 presented with isolated CNS prodromal or seizure-dominant features, five with combined CNS and cardiovascular involvement, two with isolated cardiovascular toxicity, two with atypical multisystem manifestations, and one with isolated encephalopathy without clinically seizure or hemodynamic instability. Only one prior case (29) presented with isolated encephalopathy in the absence of clinically seizure or hemodynamic instability, a pattern our case shares.

Table 2: LAST presentations in published case reports identified through targeted PubMed search.

Search strategy: PubMed searches were performed using “lidocaine associated systemic toxicity,” “bupivacaine associated systemic toxicity,” “liposomal bupivacaine associated systemic toxicity,” “ropivacaine associated systemic toxicity,” and “local anesthetic associated systemic toxicity.” The searches identified 81 records. After removal of 35 duplicate records, 46 unique publications were assessed for eligibility. Twenty-eight publications were excluded: 12 were not relevant to the clinical question, 10 did not describe confirmed local anesthetic systemic toxicity, five could not be adequately assessed because full text was unavailable or toxicity could not be confirmed, and one described a non-comparable transdermal lidocaine presentation. Eighteen publications reporting 21 LAST cases were included. The present case is displayed separately and is not included among the 21 cases identified by the literature search. Reference numbers in the author column correspond to the reference list. Highlighted row indicates the present case. ILE = intravenous lipid emulsion; TAP = transversus abdominis plane; TKA = total knee arthroplasty; RA = rheumatoid arthritis; ESP = erector spinae plane.

These findings have several important implications for the bedside recognition of LAST. Hemodynamic instability is absent in roughly half of confirmed LAST cases (12-20); anchoring on the combination of CNS and cardiovascular findings therefore delays treatment in approximately half of patients. The CNS prodrome is heterogeneous and easily mistaken for other postoperative phenomena. Hallucinations and visual disturbances (16-18), dysarthria with focal motor signs (21), perioral numbness with confusion (12), and progressive encephalopathy (29, present case) all fall within the prodromal spectrum but resemble postoperative delirium, emergence phenomena, or focal cerebrovascular events more than they resemble the textbook description of LAST. In a postoperative patient receiving sedation, analgesia, and antiemetics, these features are routinely attributed to medication effect or expected postoperative cognitive dysfunction. Seizures associated with LAST may be difficult to control and require prompt treatment with antiepileptic drugs alongside lipid emulsion therapy. Refractory seizures will remain until lipid emulsion is administered, supporting the role of lipid as both first-line treatment and diagnostic confirmation rather than a measure of last resort (1-6). The same principle may extend to non-seizure presentations: when clinical suspicion for LAST is high and alternative diagnoses have been reasonably excluded, empirical lipid emulsion should not be delayed while awaiting definitive confirmation. In our patient, the progression from hallucinations to deep encephalopathy four hours after a bupivacaine ESP block, with exclusion of imaging-detectable cerebrovascular causes, common metabolic derangements, and benzodiazepine or opioid effect, satisfied this threshold. Empirical 20% lipid emulsion administered per ASRA 2020 dosing produced prompt clinical improvement with complete recovery within 24 hours, providing additional clinical support for the diagnosis (6). Although lipid emulsion is central to the treatment of LAST, cumulative dosing should be monitored carefully. ASRA guidance recommends an upper limit of approximately 10 mL/kg of lipid emulsion during the first 30 minutes of resuscitation, while the updated 2020 checklist recommends a maximum cumulative dose of 12 mL/kg. In our 99.7-kg patient, the total administered dose was approximately 5.0 mL/kg, well below these limits (5-31). Excessive administration has been associated with severe iatrogenic hypertriglyceridemia and other complications (20). LAST should be considered when any unexplained neurological or cardiovascular change occurs within hours of local anesthetic administration, not only when both systems are involved. The diagnostic threshold should be temporal proximity to a regional block plus exclusion of alternatives, rather than the textbook combination of seizure and collapse. This posture aligns with current international guidance (5,6,10,11). More specifically, the use of liposomal bupivacaine in our patient warrants consideration, as its prolonged-release formulation may be relevant to the delayed onset of toxicity observed in this case. Exparel is a prolonged-release formulation of bupivacaine that uses DepoFoam technology, in which bupivacaine is encapsulated within micro-sized multivesicular liposomes (MVLs), allowing sustained local release for 48-72 hours. MVLs are characterized by a honeycomb-like structure, with the inner aqueous phase divided into multiple non-centric chambers that support prolonged drug release. (32) The sustained release mechanism of Exparel has been studied but is not fully understood at this time. Manna et al , proposed a triphasic release profile. The first stage consists of an initial burst release, thought to reflect unencapsulated or surface-bound bupivacaine. This is followed by a lag phase characterized by slow diffusion through lipid membranes, potentially accompanied by lipid rearrangement. A secondary release phase then occurs, largely attributed to particle erosion (33). Compared with immediate-release bupivacaine, liposomal bupivacaine produces prolonged systemic exposure and a delayed pharmacokinetic profile, which may extend the temporal window during which systemic toxicity can occur. The 20 mL Exparel formulation contains 266 mg of bupivacaine, providing a substantial amount of drug available for absorption. In this case, the patient also received 50 mg of immediate-release bupivacaine HCl with 266 mg of liposomal bupivacaine, corresponding to a bupivacaine HCl-to-Exparel ratio of approximately 1:5.3. This was within the manufacturer-recommended maximum ratio of 1:2 for concomitant administration; however, the systemic toxic effects of local anesthetics are additive. Therefore, a high index of suspicion should be maintained when new neurologic or cardiovascular abnormalities arise following regional anesthesia, particularly when no alternative explanation is apparent. Notably, current prescribing information recommends a maximum perineural Exparel dose of 133 mg for approved nerve blocks, whereas our patient received 266 mg in an off-label ESP block (35). Whether this higher perineural dose contributed to the development of systemic toxicity cannot be determined from a single case and should be explored in future studies evaluating dose-dependent systemic exposure and LAST risk with liposomal bupivacaine used in fascial plane blocks.

Use of liposomal bupivacaine for ESP block is not among the currently established regional nerve-block indications in the United States; current prescribing information limits established regional analgesia indications to interscalene brachial plexus, popliteal sciatic, and adductor canal blocks. Accordingly, the four-hour onset of neurological symptoms in our patient is biologically compatible with ongoing systemic exposure, although the temporal relationship cannot establish that the liposomal formulation itself caused the delayed or CNS-predominant phenotype. The slower release also means that it may require an extended observation. In the case we are presenting the team elected to watch the patient for a minimum of 24 hours after lipid emulsion was given to monitor for any residual signs of LAST, but none appeared. Exparel use has increased since its earlier years on market. Expanded FDA indications for its use accompanied by a strong push to focus on opioid sparing approaches to analgesia will likely increase its utilization (34). Given this information, it would be prudent to consider LAST on the differential diagnosis for many hours after a nerve block with Exparel. The prolonged-release mechanism of Exparel may have contributed to the delayed onset of symptoms in this case by extending the period of systemic bupivacaine exposure. However, whether this pharmacokinetic profile also influenced the predominantly neurologic presentation, rather than producing seizures or cardiovascular toxicity, cannot be determined from a single case.

Conclusion

LAST may present as isolated encephalopathy with hallucinations in the absence of clinically apparent seizures or cardiovascular instability, an uncommon but recognized phenotype within the published spectrum of toxicity. Because a substantial proportion of reported LAST events lack hemodynamic instability, waiting for the classic combination of CNS excitation and cardiovascular collapse may delay recognition and treatment. Following fascial plane blocks such as the ESP block, systemic absorption of local anesthetic can produce delayed neurological manifestations that may be mistaken for postoperative delirium, residual sedation, or emergence phenomena. Current guidance from major professional societies recognizes isolated, atypical, and delayed presentations of LAST. Accordingly, when LAST is strongly suspected and alternative causes have been reasonably excluded, intravenous lipid emulsion should not be delayed solely because clinically apparent seizures or cardiovascular instability are absent.

Acknowledgements: none

Funding: none

Competing Interests: The authors declare that they have no competing interests.

Patient consent: Written informed consent for publication of this case report was obtained from the patient.

Data Availability: Not applicable. No datasets were generated or analyzed for this case report. All relevant clinical information is contained within the manuscript, with identifying information omitted to protect patient confidentiality.

AI Use Disclosure

ChatGPT (OpenAI) was used to assist with language editing (grammar, flow and prose), manuscript organization, and refinement of selected sections. All clinical information, literature interpretation, references, and final manuscript content were independently reviewed and verified by the authors, who take full responsibility for the accuracy and integrity of the work.

Author contribution statement

N.K.: Conceptualization, investigation, data curation, and writing, original draft. A. C-R.: Conceptualization, methodology, literature review, data interpretation, writing, original draft, writing/review and editing, and project administration. S.V.: Supervision, clinical interpretation, and review. Gabriela Domínguez Arocho: Pharmacotherapy review, treatment-data verification, clinical interpretation, and writing, review and editing. Hillary Starling: Pharmacotherapy review, literature review related to liposomal bupivacaine and intravenous lipid emulsion, clinical interpretation, and writing, review and editing. R. H.: Conceptualization, review Y. M.: Conceptualization review, manuscript edits, supervision.

All authors reviewed and approved the final manuscript and agreed to be accountable for the accuracy and integrity of the work.

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