Bautista, Alexander Pharmacotherapy of Procedural Sedation in Morbidly

Journal of Clinical Research in Pain and Anaesthesia ISSN: 2689-6141

Mini Review Volume 2 Issue 1

Pharmacotherapy of Procedural Sedation in Morbidly Obese

Bautista Alexander1*, Liu Robert1, OngSio Lady Christine1 and Wadhwa Anupama2 1Department of Anesthesiology and Perioperative Medicine, Louisville, Kentucky, USA 2Outcomes research consortium, Presidential, international society of peri operative care of obese patients, University of California, San Diego, USA

*Corresponding author: Alexander Bautista, Department of Anesthesiology and Perioperative Medicine, 530 S Jackson St,

Louisville, Kentucky 40202, USA, Tel: 5023450273; Email: [email protected] Received Date: January 01, 2020; Published Date: January 23, 2020

Abstract

Procedural sedation in morbidly obese patients can present special challenges, because of the cardiorespiratory changes

Keywords:associated with Cardiorespiratory; morbid obesity. This Alfentanil; mini review Dexmedetomidine; presents various Remifentanil pharmacologic options available for sedation in these patients.

Abbreviations: TBW: Total Body Weight; LBW: Lean brought in part by the increased fat- and lean-body mass [2,3]. The volume of distribution of many drugs is affected, IntroductionBody Weight; GABA: G-Aminobutyric Acid. The increased prevalence of sleep apnea with concomitant carbonas well dioxide as changes retention, in tissue reduction perfusion in functional in obese patients.residual Obesity in the United States has been growing in number capacity, and cardiac dysfunction are some of the anatomic changes in obese patients that contributes to alteration in number of diagnostic and therapeutic procedures under Pharmacodynamic agents of the drugs used for procedural over the recent decades [1]. These patients present for a providing anxiolysis, analgesia, and preventing movement sedation. The goals of every procedural sedation include Pharmacokineticsedation [3]. and Pharmacodynamic the choice of drugs varies on the provider’s experience and during the most stimulating parts of the procedure. However, Principles in Obesity The increase in adiposity accounts for the pathophysiologic associatedcomfort level. with Morbid a higher obesity incidence by itself of adverse poses an respiratory increased eventsrisk of including anesthetic upper complications. airway obstruction, These obstructive patients areor These changes thereby affect the pharmacokinetic and central respiratory depression that may require some form changes and multi-organ dysfunction associated with obesity. An increase in total body weight (TBW), lean body weight pharmacodynamic of the drugs used for procedural sedation. Uniqueof airway to intervention. obese patients is the altered physiologic and anatomic changes that affects the pharmacokinetic also(LBW), increases and fat themass volume are found of distribution in obese patients. of the Theselipophilic can affect the pharmacokinetics of drugs. The increased fat mass altered including peak concentration and clearance due to physiologicproperties ofincrease the sedation in blood drugs volume [2]. Drugand cardiac distribution output is bydrugs the [4,2].degree Hence, of plasma a larger protein initial binding, loading cardiac dose output,of drugs and is necessary in obese patients. Drug distribution is also affected

Bautista Alexander, et al. Pharmacotherapy of Procedural Sedation in Morbidly Obese. J Clin Copyright © 2020 Bautista Alexander, et al. Res Pain Anaesthesia 2020, 2(1): 180018. 2 Journal of Clinical Research in Pain and Anaesthesia

Obesetissue perfusion.patients are known to have an increase in cardiac excessline agent. fat tissue Benzodiazepines in obese patients are highly increases lipophilic the correlationdrugs that output, but there has been no evidence that it alters protein act via G-aminobutyric acid (GABA)-ergic pathways. The Midazolam is one of the most extensively used drugs among There has been a direct strong correlation between the between volume of distribution and elimination half-life [4]. binding to both albumin and alpha-acid glycoprotein [5,2]. dose of midazolam, the intensity and duration of action of itsthe sedative different effects benzodiazepines. depend much Aftermore aon single the extent intravenous of drug increased cardiac output and LBW. This creates confusion as to the best parameter to follow in dosing drugs, i.e., TBW that The initial distribution half-life of midazolam ranges reflects the associated increase in volume of distribution or distribution than on the rate of elimination and clearance. Theto LBW increase to account in cardiac for the output increase in obese in cardiac patients output would [6,7,2]. also benzodiazepine used, the single intravenous dose should be basedbetween on TBW14 and while 22 forminutes continuous [4]. Regardless infusion, the of dosea particular should are also regional differences in adipose tissue perfusion andresult the in increasedsubcutaneous blood adipose flow to tissuesthe liver receive and kidneys. more Thereblood effective agents with less respiratory compromise makes the utilizationbe adjusted of based benzodiazepines on IBW. However, limited the to availabilitypremedication of other as a is an increase in drug clearance for obese patients, drug metabolismflow than abdominal and clearance and visceral is mostly fat dependent [8]. Even thoughon metabolic there Opioidssingle bolus. Pharmacotherapypathways [7,9]. Opioids are well known to contribute to upper airway Pharmacologic dosing strategies are dependent on the opioid use not suitable for situations requiring spontaneous voluntaryobstruction effort and andrespiratory those with depression. high likelihood These reasonsof respiratory make mentionedprovider’s choice above, of morbidlydrug. Drug obese regimen patients can be maya single require drug have increased incidence of obstructive sleep apnea, hypoxia, specialor a combination dosing regimen of drugs and to achieve knowledge the desired of the effect. altered As comprise such as in morbidly obese patients. Obese patients pharmacologic behavior of medication used is essential for tissue in these patients puts them at risk for upper airway and central sleep apnea. The redundant upper pharyngeal

Propofoloptimal management. obstruction [11,12]. Propofol is one of the widely utilized drugs during procedural withFentanyl caution is a potent is appropriate synthetic opioid.for painful It has procedures, a rapid onset but and a continuousshort duration infusion of action. is notAdministering recommended intermittent for procedural boluses barriersedation. and It is distribution a highly lipophilic to the with central rapid nervous onset and system, short followedduration ofby action.rapid redistributionIts rapid penetration to inactive of the tissue blood-brain depots volumesedation. of Its distribution long context-sensitive due to excess half-life adipose does tissue not in make obese it such as muscles and fat makes propofol’s duration of action a preferred agent. Also, its lipophilicity results in increased

patients [13]. Thus, it is best to dose fentanyl based on LBW lipophilic,predictable the [4]. volume Propofol’s of distribution pharmacokinetics is therefore are higher highly in Sufentanilor IBW to preventis an extremely overdosing potent and respiratory synthetic depression.derivative of dependent on cardiac output [2]. Since propofol is highly cardiac output in obese patients may contribute to the obese patients than in normal weight patients. The higher lipophilicityfentanyl. It hasis the a morereason rapid behind onset altered and pharmacokinetics shorter duration of steady-state volume and clearance with increasing total of action compared to fentanyl. Similarly, its profound increase in clearance of propofol. There is a direct correlation sufentanil may also cause severe decrease in systolic blood in obese patients. Aside from common side effects of opioids, itbody is judicious weight. Itto hastitrate been the suggested recommended that administration propofol does to of Due to its medium and long-lasting anesthetic effects, it is propofol in obese patients be based on TBW [10]. However, pressure, bradycardia, and increased intracranial pressure.

Benzodiazepineseffect in obese subjects. not ideal for procedural sedation [14]. the fastest onset of action followed by sufentanil and then Benzodiazepines have been widely used as an anxiolytic, Alfentanil is another synthetic derivative of fentanyl. It has to fentanyl and sufentanil, indicating a smaller volume of fentanyl. The lipophilicity of alfentanil is less compared but the current trend is to move the tide away as a first

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Combination drugs such as ketofol (ketamine plus propofol) action which makes it a favorable agent for short procedures and ketodex (ketamine plus dexmedetomidine) have been ordistribution when quick [15]. adjustment Alfentanil of also consciousness has a very levelshort is duration necessary of gaining popularity but most of the literature is done in the

adults and morbidly obese patients as to the appropriate [16]. Furthermore, alfentanil results in less hemodynamic pediatric population [21]. There is still paucity of data in instability compared to fentanyl and remifentanil. However, the likelihood of respiratory depression is higher. Hence, close Dexmedetomidinedosing and concomitant adverse reaction. Remifentanilmonitoring of is ventilation easy to use and due vital to signs its rapid is crucial. metabolism by tissue and plasma esterase resulting in organ-independent Dexmedetomidine is a highly selective alpha-2-agonist that has been used for procedural sedation and as an adjunct to remifentanil makes it preferable where a continuous infusion clearance [13]. The lack of context-sensitive accumulation of sedative, anxiolytic, sympatholytic properties without general anesthesia. It has been found to possess hypnotic, is required. The short duration of action of remifentanil opioid sparing effect of dexmedetomidine without causing Ketamineallows it to be dosed on lean body mass [17]. respiratoryproducing significantdepression respiratoryhas increased depression its popularity [3,22]. to The be The use of ketamine has been widely used in pediatric population and procedural sedation done in the emergency used in bariatric surgery [23]. The systemic disposition of dexmedetomidine is significantly altered in morbidly obese has been suggested that ketamine may have a place in Thepatients. clearance of dexmedetomidine predominantly depends analog-sedationroom. In a systematic for adults review due doneto its byopioid-sparing Laskowski et.al, effect it lower clearance in obese patients compared to patients sympathomimetic and is associated with hallucinations, on hepatic blood flow and Xu, et al. showed significantly however[18]. It should small doses be noted used that for sedation higher dose between of ketamine 10-50 mg is ug/kg/hr has been recommended to avoid bradycardia with normal body mass index [22]. An infusion rate of 0.2 and oxygen saturations were still lower in morbidly obese Aare combination not associated of ketamine with these and side benzodiazepine effects. or propofol and hypotension [2]. However, sedation levels were deeper careful attention should be paid when dexmedetomidine is depression is low and has been reported to be a protective patients than in normal body weight patients [22]. Hence, factormay reduce for sedation-related the risk of hallucination. airway events The risk by ofreducing respiratory the amount of other sedative agents needed to achieve the same used. To date, there is still paucity of data to guide therapy in Conclusionmorbidly obese patients. effect [19]. In general, the newer, S-ketamine form has a better tolerability profile than the racemic form [20]. formal study that has been conducted to evaluate which choiceSignificant of pharmacotherapy challenges exist in used the managementin sedation canof morbidly directly dosingKetamine should is dosed be utilized based in upon obese TBW. patients However, for procedural there’s no obese patients presenting for procedural sedation. The pharmacokinetic parameters of drugs used for sedation, hence can lead to higher rate of adverse effect such as over-sedation drugimpact dosing the success must be of based the procedure on the volume itself. ofObesity distribution alters thefor sedation. However, it should be noted that increasing dosage it is imperative to preserve good practice and risk reduction or respiratory depression, if combined with opioids. Under duringthe loading the conductdose and of on the clearance sedation for in maintenance. this subset of However, patients dosing, on the other hand, may lead to decreased efficacy or may need additional sedative agents. (Table 1). Drugs Bolus Dose Maintenance Dose Weight for Dosing Elimination half-life (TBW,IBW, LBW) Propofol 50-200 mcg/kg/min TBW 4-7 hrs Midazolam TBW (single dose) 0.5-1 mg/kg 0.01-0.1 mg/kg 0.02-0.1 mg/kg/hr 1.7-2.6 hrs Fentanyl 10-20 mcg/kg 2-50 mcg/kg LBW IBW (continuous) Sufentanil LBW 6-9 hrs 8-10 hrs 0.2-0.4 mcg/kg 0.20-1 mcg/kg/hr

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Alfentanil 70-99 mins Remifentanil LBW 3-10 mins 8-100 mcg/kg 0.5-3 mcg/kg/min IBW min 0.05-0.3 mcg/kg/ 0.05-2 mcg/kg/min Ketamine TBW Dexmedetomidine 1 mcg/kg over 10 LBW 0.1-0.4 mg/kg 0.1-1 mg/kg/hr 2.5 hrs mins 0.2-1.4 mcg/kg/hr 2.1-3.1 hrs Table 1:

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