Efficacy of intravenous lipid emulsion in enhancing the recovery of spinal anesthesia: An exploratory double-blinded, randomized controlled study

Abstract

Purpose:

Prolonged motor recovery associated with spinal anesthesia (SA) limits its utility in day-case surgery. We evaluated the efficacy of intravenous lipid emulsion (ILE) in accelerating recovery from sensory-motor blockade in patients undergoing day-case surgery under SA.

Methods:

In a double-blinded randomized study, 60 adult patients who underwent short surgical procedures under SA were randomly allocated to receive either ILE (1.5 mL/kg bolus, followed by 0.25 mL/kg/min infusion) over 30 minutes (test group) or normal saline (control group) in the immediate postoperative period. The primary objective was the time to recovery of sensory and motor blockade. The study was registered in the clinical trial registry of India CTRI/2021/11/038080 dated 11/6/2021 (www.ctri.nic.in).

Results:

Demographic characteristics (age, gender, American Society of Anaesthesiologists physical status grading, height, and weight) were comparable between the two groups. The recovery of sensory (200.6 ± 19.8 min versus 237.1 ± 17.9 min, P ≤ 0.001, absolute standard difference: -−1.9 (95% confidence interval [CI]: -−2.5 to -−1.3) and motor block (157.8 ± 13.1 min versus 193.6 ± 23.0 min, P ≤ 0.001, absolute standard difference: -−1.9 (95% CI: -−2.5 to -−1.3) were significantly faster in the test group compared to the control group.

Conclusions:

This study demonstrates that 20% ILE accelerates recovery from SA (both sensory and motor blocks), highlighting its potential utility in day-case surgery. Further trials on a larger sample size are required to validate the same.

Trial Registration: CTRI/2021/11/038080 dated 11/6/2021.

Introduction

Day-case surgical procedures aim to facilitate a quicker return to regular activities, thereby enhancing patient satisfaction, lowering hospital costs, and reducing the risk of nosocomial infections.[1] Spinal anesthesia (SA) is well-suited for lower limb and lower abdominal day-case surgeries because it eliminates the need for airway management. However, prolonged motor recovery following this procedure can delay the patient’s ability to walk, thereby undermining the benefits of day-case surgery.[2] No established strategy could accelerate the recovery from a prolonged motor blockade.

Multiple professional societies (American Heart Association, American Society of Regional Anaesthesia) recommend using intravenous lipid emulsion (ILE) as a first-line treatment for local anesthetic systemic toxicity (LAST).[3,4] The ability of ILE to accelerate the recovery of unintended peripheral nerve and central neuraxial blockades[5,6,7,8] has sparked interest in exploring its utility in SA for day-case surgery. The mechanism by which it accelerates the recovery of local anesthetic effects is more intricate than a simple partitioning or the “sink” effect. It involves multiple scavenging and nonscavenging pathways. The scavenging actions include removing drugs from critical organs and modulating metabolic and signaling pathways to protect against ischemic damage. The nonscavenging effects include cardiotonic and vasoconstrictive actions that enhance tissue perfusion.[9,10]

We hypothesized that ILE could expedite the neuraxial recovery from SA. We evaluated the efficacy of ILE as a reversal agent in reducing the duration of sensory-motor blockade in patients undergoing day-case surgery under SA. Any associated complications and postoperative pain scores were also noted.

Methods

After Institute Ethical approval (AIIMS/IEC/21/314 dated 13/8/2021) and registration with the clinical trial registry-India (CTRI/2021/11/038080 dated 11/6/2021, www.ctri.nic.in). In this prospective, double-blinded, randomized controlled pilot study, we included 60 patients aged > 18 years, of either gender, with American Society of Anaesthesiologists Physical Status (ASA-PS) I or II, who were scheduled for any elective short-duration day-case surgical procedure under SA after written informed consent between June 2021 and November 2022 at a tertiary care hospital in India. The study was conducted in accordance with the Declaration of Helsinki, and the results were reported in accordance with the Consolidated Standards of Reporting Trials (CONSORT) statement. Patients with any contraindications for SA, severe systemic disease, or any comorbidity that interferes with outcomes assessment were excluded.

The patients were randomly assigned to either of two groups: the test group (20% ILE) or the control group (normal saline), using a computer-generated random number table concealed in sequentially numbered, sealed envelopes. The study drugs were prepared in an infusion pump by an anesthesiologist, blinded to patient management and outcome parameters. The patient and the supervising anesthesiologist remained blinded to group allocation. The outcome parameters were recorded by an investigator blinded to other aspects.

All patients were duly informed about the procedure during the preanesthetic assessment. On arrival at the operating theater, standard American Society of Anaesthesiology (ASA) monitors were attached (electrocardiogram [ECG], non-invasive blood pressure, and pulse oximetry [SpO₂]). An 18/20 G intravenous (IV) line was secured, and a crystalloid preload (500 mL) was performed. Under aseptic precautions, all patients received SA (0.5% hyperbaric bupivacaine, 3 mL) in a sitting position, at L3-4 vertebral level (confirmed by palpation), using a 25G Quincke’s spinal needle. The level of sensory blockade (mid-nipple line for T4, xiphisternum for T6, umbilical line for T10, halfway between xiphisternum and umbilical line for T8, etc.) was assessed with a cold swab and motor blockade using a modified Bromage scale (MBS) every 5 minutes for the first 15 minutes, respectively. The surgery was allowed to commence once the T10 dermatomal level was achieved. All patients were continuously monitored for hemodynamic changes during the surgical procedure. Any hypotensive episode (mean arterial pressure [MAP < 65 mm Hg] was treated with a fluid bolus and, if necessary, IV phenylephrine (25 µg). Bradycardia (heart rate [HR] <50 beats/min) was treated with an IV bolus of atropine 0.5 mg. The sensory-motor block levels were again noted at the end of surgery. Thereafter, all patients received study drugs as per group allocation; the test group received 20% ILE bolus (1.5 mL/kg IV over 3 minutes), which was administered inside the operating theater, and after shifting the patient to the postoperative care unit (PACU), ILE was administered at 0.25 mL/kg/min infusion over 30 minutes. The control group received an equal volume of Normal Saline (NS) in a blinded manner. Sensory-motor block recovery was assessed every 15 minutes until sensory recovery to S2 dermatome and motor recovery to MBS of 6 during the PACU stay. IV paracetamol 1 gm was administered every six hours for postoperative pain management. The patients were continuously monitored for any associated complications (cardio-respiratory) during the study duration.

The sample size was estimated using G*Power. Considering an exploratory study design, we assumed a medium study effect size of 0.5 (Cohen’s d), with 90% power and a 5% significance level (alpha = 0.05), to ensure a strong probability of identifying actual effects and minimizing the risk of Type I errors.[11] This yielded a sample size of 31 per group (62 participants) after accounting for a 5% dropout rate. Statistical analysis was performed using IBM SPSS Statistics version 23(IBM Corp). Data were compiled in an MS Excel worksheet and assessed for normality using the Shapiro-Wilk test. The Wilcoxon test was used to compare continuous variables. Discrete variables (side-effects) were compared using Fisher’s exact test/Chi-square test, whichever was appropriate. P-value of <0.05 was considered significant.

Results

Sixty patients were included, with no dropouts [Figure 1]. The baseline demographic and surgical characteristics were comparable between the two groups; predominant comorbidities included diabetes and hypertension, and most cases had a urinary bladder mass (78%). They were posted for transurethral resection of the prostate [Table 1].

Figure 1.

Consolidated Standards of Reporting Trials (CONSORT) flowchart

Table 1.

Comparison of demographic and surgical characteristics

Variable	Test group (n=29)	Control group (n=31)	Absolute standardized difference (95% CI)	P
Age (Years)	40.90±12.28	41.71±10.43	-0.072 (-0.578 to 0.435)	0.783
Gender (M/F) (n)	25/4	23/8	-	0.245
ASA (I/II) (n)	16/13	16/15	-	0.782
Height (cm)	164.51±7.13	163.65±8.90	0.108 (-0.399 to 0.614)	0.678
Weight (kg)	59.34±7.23	59.29±8.91	0.007 (-0.500 to 0.513)	0.979
BMI (Kg/m2)	21.89±1.97	22.04±1.98	-0.074 (-0.581 to 0.432)	0.774
Commodities (n) (none/HT/DM)	15/9/5	17/13/1	-	0.233
Duration of Surgery (Minutes)	29.21±2.91	29.35±3.12	-0.171 (-0.677 to 0.337)	0.511
Duration of anesthesia (minutes)	34.21±2.91	34.35±3.12	-0.171 (-0.677 to 0.337)	0.511
Diagnosis (n, %)			-	1.000
UB Mass	21 (77.8)	20 (74.1)	-
Urethral Stricture	3 (11.1)	4 (14.8)	-
Urethral Mass	3 (11.1)	3 (9.6)	-
BPE/USD	2 (6.8)	4 (14.8)	-
Surgery (n, %)			-	1.000
TURBT	21 (72.4)	20 (64.5)	-
OIU	3 (10.3)	4 (12.9)	-
CPE/ENDO CLT	3 (10.3)	3 (9.6)	-
TURP/URSL	2 (6.8)	4 (12.9)	-

UB=Urinary bladder, BPE=Benign prostatic enlargement, USD=Urinary stone disease, TURBT=Transurethral resection of bladder tumor, OIU=Optical internal urethrotomy, CPE=Cysto-pan endoscopy, Endo CLT=Endoscopic cysto-lithotripsy, TURP=Transurethral resection of prostate, URSL=Ureteroscopy and laser stone fragmentation, CI=Confidence interval

Values are presented as mean±standard deviation or number (%) as appropriate

*Standardized difference was calculated using Cohen d, and mean or proportion differences were divided by the pooled standard deviation. (Cohen, J. Statistical Power Analysis for the Behavioral Sciences. 2^nd ed, Hillsdale, NJ: Lawrence Erlbaum Associates, Publishers; 1988.)

The intraoperative neuraxial block characteristics were comparable between the groups, with sensory block reaching T6-T8 dermatomal level and MBS of 1 at 15 minutes after initiation of SA [Table 2]. The mean surgical duration was comparable between the groups [Table 1]. The sensory block levels at the end of surgery ranged from T6 to T10, while MBS was 1, though comparable between groups [Table 2].

Table 2.

Intraoperative sensory level of spinal anesthesia

Parameters	Test Group (n=29)	Control Group (n=31)	Mean Difference (95% CI)	P
Sensory Blockade Level at 5-minute (n/%)				0.645
T6	0 (0.00)	0 (0.00)	-	1.000
T7	0 (0.00)	0 (0.00)	-	1.000
T8	0 (0.00)	0 (0.00)	-	1.000
T9	0 (0.00)	0 (0.00)	-	1.000
T10	18 (62.07)	21 (67.74)	-5.67% (-100.00% to 18.47%)	0.788
T11	0 (0.00)	0 (0.00)	-	1.000
T12	11 (37.93)	10 (32.26)	5.67% (-100.00% to 29.81%)	0.788
Sensory Blockade Level at 15 Minutes (n/%)				0.096
T6	6 (20.69)	14 (45.16)	-24.47% (-100.00% to -1.57%)	0.058
T7	0 (0.00)	0 (0.00)	-	1.000
T8	18 (62.07)	15 (48.39)	13.687% (-100.00% to 38.61)	0.312
T9	0 (0.00)	0 (0.00)	-	1.000
T10	5 (17.24)	2 (6.45)	10.79% (-100.00% to 27.03%)	0.247
T11	0 (0.00)	0 (0.00)	-	1.000
T12	0 (0.00)	0 (0.00)	-	1.000
Sensory blockade level at the end of surgery (n/%)				1.000
T6	9 (33.33)	13 (41.94)	-8.60% (-100.00% to 18.01%)	0.575
T7	0 (0.0)	0 (0.0)	-	1.000
T8	18 (61.90)	17 (54.84)	7.07% (-100.00% to 34.24%)	0.776
T9	0 (0.0)	0 (0.0)	-	1.000
T10	2 (4.76)	1 (3.23)	1.54% (-100.00% to 12.57%)	1.000
T11	0 (0.0)	0 (0.0)	-	1.000
T12	0 (0.0)	0 (0.0)	-	1.000

T=Thoracic dermatome level, CI=Confidence interval

The ILE group exhibited a significant early recovery of both sensory (ILE: 200.69 ± 19.81 min, control: 237.10 ± 17.92 min) and motor blockade (ILE: 157.76 ± 13.06 min, control: 193.55 ± 23.03 min), post-infusion of studied drugs [Table 3, Figure 2]. The power analysis of the time required for sensory and motor recovery yielded a high-power value of 99%. This indicates that the study was adequately powered to detect statistically significant differences in these outcomes, enhancing the reliability of the findings. None of the patients exhibited significant complications during the perioperative period [Figures 3 and 4]. The pain scores were also comparable between the groups during the postoperative period [Figure 5].

Table 3.

Spinal anesthesia recovery characteristics

Parameters (Mean±SD)	Test group	Control group	Absolute standardized difference (95% CI)	P
Full Sensory Recovery (till S2 dermatome) from the end of surgery (min)	200.69±19.81	237.10±17.92	-1.931 (-2.541 to -1.309)	<0.001
Full Motor Recovery from the end of surgery (Min)	157.76±13.06	193.55±23.03	-1.895 (-2.501 to -1.277)	<0.001

CI=Confidence interval, SD=Standard deviation

Figure 2.

The motor regression (modified Bromage scale) over time in both group

Figure 3.

Comparison of heart rate during the postoperative period

Figure 4.

Change in mean arterial pressure (MAP) during the postoperative period

Figure 5.

Comparison of pain scores (NRS) in the immediate postoperative period

Discussion

We observed a faster neuraxial recovery in patients who received 20% ILE compared with the control group, with no untoward side-effects, in both sensory and motor functions. This highlights its potential novel application for enhancing neuraxial recovery following regional anesthesia, particularly in day-case surgeries where rapid ambulation and consequent turnover are desirable.

The literature shows the use of 20% ILE, primarily as a life-saving intervention for managing LAST, concurrently resulting in the recovery of peripheral nerve/central neuraxial blocks.[12] Kamel et al. reported a simultaneous recovery of peripheral nerve block along with LAST signs following administration of ILE in a patient who received excessive local anesthetic infiltration (80 mL of 0.5% bupivacaine) for genital prolapse.[5] Similarly, Gupta et al. and Turner et al. reported two cases of interscalene blocks complicated by total SA.[6,7] The patients developed mydriasis, paralysis of all extremities, and respiratory arrest. Both patients received 20% ILE along with standard airway, breathing, and circulation management and subsequently recovered from neurological conditions. Torrie et al.[8] reported a case of LAST in a patient who received an interscalene brachial plexus block for shoulder arthroscopy. The author observed a simultaneous complete recovery of sensory and motor blockade of the upper limb and symptoms of LAST within a short period of ILE administration.

The above reports collectively suggest that ILE not only reverses systemic toxic effects but may also expedite the recovery from local anesthetic (LA)-induced nerve blocks. The findings from our study align with these anecdotal reports and extend the application of ILE beyond LAST, demonstrating its utility in routine clinical practice for accelerating SA recovery. Unlike these case reports, our study provides a controlled comparison, offering stronger evidence for the utility of ILE in enhancing neuraxial recovery after SA.

The precise mechanism by which ILE accelerates LA recovery remains to be fully elucidated. Several hypotheses have been proposed: ILE may enhance fatty acid oxidation, providing an alternative energy source for neurons affected by local anesthetics, or it may exert a cardiotonic effect that improves overall hemodynamics, indirectly aiding recovery. The scavenging effects of ILE could have contributed to the early recovery of SA 9, 10, but the exact mechanism of SA’s early recovery warrants further investigation.

Regarding safety, no adverse effects attributable to ILE were observed in our study during the immediate postoperative period. This finding is consistent with existing literature, which indicates that complications related to ILE, such as pancreatitis, hypertriglyceridemia, and fat overload syndrome, are rare.[3,13] However, clinicians should remain vigilant for these potential complications, especially in patients with underlying metabolic disorders or those requiring repeated doses of ILE. ILE is known to have a cardiotonic and vasoconstrictor/volume effect. However, we did not find any difference in hemodynamics between the groups after administration of study drugs.[3]

The current study has several limitations. First, the study population consisted of healthy patients (ASA I and II), limiting the generalizability of the findings to vulnerable populations, including those with significant comorbidities or hemodynamic instability. Second, the small sample size and single-center design may limit the robustness of the conclusions, and the results may be statistically significant, though not clinically significant. Additionally, while the study was designed to minimize observer bias, the distinct appearance of ILE could have been noticed by clinicians despite efforts to blind the study drug, potentially influencing outcomes. The study noted that only time was available to achieve full motor recovery of the lower limbs but not to ambulate.

In conclusion, 20% of ILE offered an early postoperative recovery of sensory-motor functions after SA. While promising, these results must be interpreted cautiously and are open to further validation. It can be an essential strategy to optimize patient recovery, particularly in ambulatory surgical settings.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.