OBJECTIVES: This systematic review compiles the existing knowledge on lidocaine's PK properties and published popPK models, with a focus on significant covariates.
METHODS: A systematic search on Cochrane CENTRAL, Medline, and EMBASE was performed from inception to June 2023. Original clinical studies that administered IV lidocaine to adults and performed PK analyses using a nonlinear mixed effects modelling approach were included. The quality of the included studies was assessed by compliance with the Clinical Pharmacokinetics (ClinPK) statement checklist.
RESULTS: Seven studies were included, which involved a diverse adult population, including both volunteers and patients with various comorbidities. Lidocaine PK was primarily characterised by a two- or three-compartment model. The volume of distribution at steady state ranged from 66 to 194 L, and the total clearance ranged from 22 to 49 L/h. Despite adjusting for significant covariates like heart failure status, alpha-1-acid glycoprotein, duration of lidocaine infusion, and body weight, each study revealed substantial variability in PK parameters. The potential impact of hepatic or renal function biomarkers on these PK parameters calls for further investigation. Incomplete reporting of key aspects of developed models may hinder the models' reliability and clinical application.
CONCLUSION: The findings emphasise the importance of tailoring drug dosage to ensure the safe and effective use of intravenous lidocaine. Optimal design methodologies may be incorporated for a more efficient identification of important covariates. Utilising contemporary model evaluation methods like visual predictive checks and bootstrapping would enhance the robustness of popPK models and the reliability of their predictions. This comprehensive review advances our understanding of lidocaine's pharmacokinetics and lays the groundwork for further research in this critical area of perioperative pain management. Review protocol registered on 25 August 2023 in PROSPERO (CRD42023441113). This work was supported by the Fundamental Research Grant Scheme, the Ministry of Higher Education, Malaysia (FRGS/1/2020/SKK01/UM/02/2).
METHODS: Thirty-four donor nephrectomy and 64 cholecystectomy patients received intraoperative IV lidocaine. Plasma samples were collected perioperatively and analysed in NONMEM. Covariate effects and alternative dosing regimens were investigated.
RESULTS: 1,520 concentration-timepoints were analysed. Lidocaine PK was best fitted with a 3-compartment model, while MEGX and GX used a 2-compartment model. All parameters were scaled allometrically with total body mass and fat-free mass (FFM). Lidocaine had a typical clearance of 45.9 L/h, decreasing by 60% postoperatively, and a central volume of 25.2 L. Peripheral compartments 1 and 2 exhibited intercompartmental clearances of 142 L/h and 5.81 L/h, with volumes of 44.4 L and 29.3 L, respectively. Peripheral compartment 1's volume expanded with intraoperative fluid administration. Simulations suggested an FFM-based dosing regimen (bolus: 2.5 mg/kg over 30 min, single infusion: 2 mg/kg over 1 h, maintenance infusion: 1.5 mg/kg/h) quickly achieved and maintained a lidocaine target plasma concentration of 1.5 mg/L.
CONCLUSIONS: The joint parent-metabolites model adequately describes the disposition of lidocaine and its metabolites, incorporating allometric scaling and key covariates. It provides a foundation for optimising lidocaine dosing and guiding investigations to establish target plasma concentrations for safe and effective use in the general surgical population. Further research is warranted to refine and evaluate the model's utility in other surgical populations.
METHOD: This qualitative study involved four trained researchers conducting in-depth interviews (IDI) based on a semi-structured interview guide. The participants were ICU patients and family members. All IDIs were audio-recorded and transcribed verbatim. Four researchers independently analyzed the data via thematic analysis with the aid of QDA Miner Lite®. The themes and subthemes were generated and confirmed by literature and expert opinion.
RESULTS: Six IDIs were conducted with three patients and three family members, whose ages ranged from 31 to 64 years old. One pair of participants consisted of a patient and his respective family member, while the other four participants did not have a familial relationship with each other. Three main themes emerged from the analysis: (I) critical care services; (II) physical spaces; and (III) monitoring technology. Medical, psychological, physical, and social needs for critical care services were expressed by both patients and family members. Patients' needs in clinical spaces were highlighted as a conducive ICU environment with ambient temperature and controlled noise levels. In non-clinical spaces, family members expressed a need for more chairs in the waiting area. Participants expressed the need for call bells as well as patients' negative perceptions of medical equipment alarms in the ICU when it pertained to monitoring technology.
CONCLUSION: This study provides an in-depth view at the needs and experiences of ICU patients and family members who have a variety of unmet needs. This understanding is critical for guiding ICU personnel and stakeholders in their efforts to humanize ICU care.