เภสัชบำบัดและการประยุกต์ใช้ยาสลบชนิดไอระเหยเพื่อการสงบระงับในผู้ป่วยวิกฤต Pharmacotherapy and Application as Inhaled Anesthetics for Critically Ill Patients

บทคัดย่อ ผู้ป่วยที่รักษาตัวในหอผู้ป่วยวิกฤต (intensive care unit; ICU) มักประสบกับความปวดและภาวะกายใจไม่สงบ จำเป็นต้องได้รับยาระงับปวดร่วมกับยาสงบระงับชนิดบริหารทางหลอดเลือดดำหลายชนิดเพื่อลดความปวด ลดภาวะกายใจไม่สงบ และลดโอกาสเกิดอาการไม่พึงประสงค์ที่เกิดจากยาโดยอาศัยหลักการ analgosedation ในการดูแลผู้ป่วย เพื่อให้ผู้ป่วยวิกฤตที่มีข้อจำกัดดังกล่าวสามารถคงภาวะสงบระงับอยู่ในช่วงเป้าหมายอย่างมีประสิทธิภาพ และปลอดภัย ในทางคลินิกปฏิบัติ ยาสลบชนิดไอระเหยมักถูกเลือกใช้ในผู้ป่วยวิกฤตที่มีปัญหาการทำงานของตับและไตบกพร่อง โดยนำยาสลบชนิดไอระเหยมาใช้ในหอผู้ป่วยวิกฤต ยาสลบชนิดไอระเหยช่วยลดระยะเวลาในการหย่าเครื่องช่วยหายใจในเวลาที่สั้น ลดการใช้ยากลุ่มอนุพันธ์ฝิ่น (analgesic sparing effect) ลดการใช้ยาหย่อนกล้ามเนื้อ ทำให้ระยะเวลาฟื้นตัวรวดเร็วขึ้น รวมถึงลดการเกิดภาวะกายใจไม่สงบในผู้ป่วยวิกฤต เนื่องจากยาสลบชนิดไอระเหยนี้ถูกขจัดออกจากร่างกายผู้ป่วยผ่านทางปอดในช่วงขณะหายใจออก จึงทำให้ยาสลบชนิดไอระเหยนี้ไม่สะสมในร่างกาย  ดังนั้นทีมผู้ให้การรักษา โดยเฉพาะอย่างยิ่งเภสัชกรที่ให้การบริบาลทางเภสัชกรรมแก่ผู้ป่วยวิกฤต ควรมีความรู้ ความเข้าใจทางเภสัชบำบัด เภสัชจลนศาสตร์ เภสัชพลศาสตร์ในการใช้ยาสลบชนิดไอระเหยเพื่อการสงบระงับในผู้ป่วยวิกฤตได้อย่างเหมาะสม โดยมุ่งหวังให้ผู้ป่วยได้รับยาที่มีประสิทธิภาพ ความปลอดภัย และสามารถผ่านพ้นภาวะวิกฤตได้ คำสำคัญ: เภสัชบำบัด; ยาสลบชนิดไอระเหย; การสงบระงับ; ผู้ป่วยวิกฤต Abstract Most critically ill patients admitted to the intensive care unit (ICU) experience and suffer pain and agitation; therefore, intravenous analgesics and sedatives are required. According to the analgosedation regimens, incorporating multimodal analgesia and sedatives may optimize pain and agitation management. It may also decrease the use of opioids and sedatives, thereby reducing the risk of associated adverse effects. However, in clinical practice, the use of sedation is limited in some critically ill patients who experience adverse reactions. Thus, inhalational anesthetics are alternatively applied for ICU sedation in critically ill patients to maintain the therapeutic target of sedation for optimal care during the critical period. In clinical practice, inhalational anesthetics are now widely used as sedation in intensive care, especially in critical care patients who have impaired renal and liver function. Inhalational anesthetics are independently exhaled by the lungs and require minimal metabolism. Its advantages include that inhaled sedation reduces the extubation and weaning times of mechanical ventilation, lowers opioids (analgesic sparing effect) and muscle relaxant use, enhances recovery, and minimizes delirium. The multidisciplinary team especially the pharmacists providing pharmaceutical care to critically ill patients should understand the intricate pharmacotherapy, pharmacokinetics, and pharmacodynamics of inhalational anesthetics to optimize and personalize these medications for these patients. Keywords: inhalational anesthetics; sedation; critically ill patient

The potential risk of ventilator-induced lung injury from five different PEEP titration techniques in ARDS

IntroductionThe optimal positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) remains uncertain. This study compared the PEEP levels using five distinct titration methods to assess potential ventilator-induced lung injury (VILI).MethodsThis study included 21 patients with moderate to severe ARDS who were monitored using esophageal balloon manometry and electrical impedance tomography (EIT). A recruitment maneuver followed by decremental PEEP titration was performed. Optimal PEEP (OP) was assessed using five criteria: highest respiratory system compliance (CRS), highest lung compliance (CL), end-expiratory transpulmonary pressure (Ptp_ee_direct) ≥ 0 cm H2O, elastance-derived end-inspiratory transpulmonary pressure (Ptp_ei_derived) ≤ 25 cm H2O, and EIT-based analysis balancing the degree of overdistention and lung collapse.ResultsSignificant differences in OP were observed across the methods (p = 0.001): CRS 8.0 cmH₂O (8.0,13.9); CL 9.8 cmH₂O (8.0,14.0); Ptp_ee_direct ≥ 0 cmH₂O 14.0 cm H₂O (11.9,17.9); Ptp_ei_derived ≤ 25 cmH₂O 12.0 cmH₂O (10.0,13.9); EIT balancing the degree of overdistention and lung collapse 13.01 cmH₂O (9.88,14.78). The OP guided by Ptp_ee_direct of ≥ 0 cm H2O is significantly higher than OP by the highest CRS (p = 0.001) and the highest CL (p = 0.002), and met the overdistension criteria, namely plateau pressure > 30 cm H2O and the highest percentage of overdistension by EIT. The PEEP guided by CRS had a higher potential risk of lung collapse, reflected by the negative value of Ptp_ee_direct and a higher percentage of lung collapse by EIT.ConclusionTranspulmonary pressure-guided PEEP titration yielded higher PEEP levels, while CRS-guided PEEP was lower and associated with a higher risk of collapse. Overdistension and collapse varied with the chosen PEEP method. In patients with moderate to severe ARDS, OP can vary depending on the method of assessment

Anti-inflammatory agents other than corticosteroid in SARs-CoV-2 pneumonia

The SARs-CoV-2 results in hyperinflammation among infected patients. This condition leads to serious organ injury, especially in the lungs. Therefore, the main treatment option, in addition to anti-viral agents, is the administration of corticosteroids. However, in many cases, inadequate response to corticosteroids has been observed—other anti-inflammatory agents, such as interleukin-6 inhibitor, kinase inhibitor, etc., play an essential role in reducing this severe complication.</jats:p

An importance of respiratory drive and effort during mechanical ventilation

During mechanical ventilation, minimizing respiratory drive and effort becomes routine to prevent patient-ventilator asynchrony (PVA). As we know, PAV associates with poor outcomes in ICU patients. As a result, prescribing sedative drugs in combination with neuro-muscular blocking agents commonly appears in many ICUs. However, many patients develop adverse events from unloading respiratory muscles, resulting in prolonged mechanical ventilator and bad clinical outcomes. This review describes both sides of the adverse effect of respiratory drive and effort and tries to suggest the optimum point, believing that it may be associated with better outcomes.</jats:p

The characteristics of the continuously-recorded mechanical power and its associated clinical outcomes in medical patients with respiratory failure (CORE POWER) study: The protocol of prospective observation study.

Background: The amount of energy delivered from the ventilator applied to the lungs within a given timeframe, is defined as mechanical power (MP). Recently, low MP is one of the new concepts in lung-protective ventilation strategies that may associate with survival benefit. However, measuring MP requires additional calculations not being carried-out in usual clinical care and the reports about MP were mostly a cross-sectional data. The real-time changes or dynamic data of MP was scarcely reported. Our objective is to investgate the association between the dynamic changes of MP and clinical outcomes in critically ill patients. Methods: This will be a prospective, observational study performed in a single center. Adult patients admitted to medical intermediate and intensive care units who requiring invasive mechanical ventilation will be consecutively enrolled. The patients’ ventilators will be connected to the specific investigator’s computer system for continuously real-time data recording for at least 24 hours. The primary outcome is in-hospital mortality. Hypothesis: We hypothesize that excessive mechanical power during mechanical ventilation contributes to ventilator-induced lung injury, thus real-time continuously mechanical power monitoring may reduce adverse events associated with mechanical ventilation. Ethic: The study protocol has been approved by the Institution Review Board of Ramathibodi Hospital, Mahidol University, Thailand (No. MURA2021/680). Trial registration: TCTR20220202010</jats:p

Effective Arterial Elastance as The Best Predictor of Mean Arterial Pressure in Patients with Sepsis or Septic Shock Receiving Fluid Expansion: A Validation Study by Regression Analysis

Abstract Backgroundwe conducted this study to compare four arterial load parameters and determine which arterial load parameters directly impacted arterial pressure regarding pressure, flow, and arterial system relationship.MethodsWe conducted a cross-sectional study in patients with sepsis who underwent volume expansion (VE). Hemodynamic parameters were recorded before and after VE. The relationship between the change of mean arterial pressure (%MAP) and that of the dynamic arterial elastance (EaDyn), effective arterial elastance (Eaeff), net arterial elastance (EaNet), and net arterial resistance (RaNet) was analyzed.ResultsSixty-two patients were included. The DEaDyn(%) was not correlated with DMAP(%) (r=0.048, P=0.826). Meanwhile, DEaeff(%), DEaNet(%), and DRaNet(%) were correlated with DMAP(%) (r=0.495, P&lt;0.001; r=0.453, P&lt;0.001; and r=0.485, P&lt;0.001, respectively). A multiple linear regression model was analyzed for identifying predictors of DMAP(%) by including DCO(%) and each %change of arterial parameters. The best-fit model was found by including DCO(%) and DEaeff(%) in the regression equation (R2=0.823, adjusted R2=0.817). The model was adjusted by age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, arterial lactate level, norepinephrine dosage, ventilator setting, method of VE, and fluid responsiveness and found that DCO(%) and DEaeff(%) remained statistically significant predictors of DMAP(%) (P&lt;0.001 and P&lt;0.001, respectively).ConclusionThe Eaeff was the best AL parameter that correlated with the changes in MAP. Furthermore, the model that included the ∆Eaeff(%) provided the best predictive performance for ∆MAP(%) induced by VE, independent of the fluid responsiveness and norepinephrine dosage.</jats:p