Analgo-sedation in Patients on Non-invasive Mechanical Ventilation: Need for Guideline Recommendation.

Shrinath V, Marwah V, Jyothis MC. Analgo-sedation in Patients on Non-invasive Mechanical Ventilation: Need for Guideline Recommendation. Indian J Crit Care Med 2024;28(3):309-310.

Effects of Ketamine Infusion on Breathing and Encephalography in Spontaneously Breathing ICU Patients.

BACKGROUND: Preclinical studies suggest that ketamine stimulates breathing. We investigated whether adding a ketamine infusion at low and high doses to propofol sedation improves inspiratory flow and enhances sedation in spontaneously breathing critically ill patients. METHODS: In this prospective interventional study, twelve intubated, spontaneously breathing patients received ketamine infusions at 5 mcg/kg/min, followed by 10 mcg/kg/min for 1 h each. Airway flow, pressure, and esophageal pressure were recorded during a spontaneous breathing trial (SBT) at baseline, and during the SBT conducted at the end of each ketamine infusion regimen. SBT consisted of one-minute breathing with zero end-expiratory pressure and no pressure support. Changes in inspiratory flow at the pre-specified time points were assessed as the primary outcome. Ketamine-induced change in beta-gamma electroencephalogram power was the key secondary endpoint. We also analyzed changes in other ventilatory parameters respiratory timing, and resistive and elastic inspiratory work of breathing. RESULTS: Ketamine infusion of 5 and 10 mcg/kg/min increased inspiratory flow (median, IQR) from 0.36 (0.29-0.46) L/s at baseline to 0.47 (0.32-0.57) L/s and 0.44 (0.33-0.58) L/s, respectively (p = .013). Resistive work of breathing decreased from 0.4 (0.1-0.6) J/l at baseline to 0.2 (0.1-0.3) J/l after ketamine 10 mcg/kg/min (p = .042), while elastic work of breathing remained unchanged. Electroencephalogram beta-gamma power (19-44 Hz) increased compared to baseline (p < .01). CONCLUSIONS: In intubated, spontaneously breathing patients receiving a constant rate of propofol, ketamine increased inspiratory flow, reduced inspiratory work of breathing, and was associated with an "activated" electroencephalographic pattern. These characteristics might facilitate weaning from mechanical ventilation.

A comparative study of sedo-analgesic effect of dexmedetomidine and dexmedetomidine with ketamine in postoperative mechanically ventilated patients.

Background and Aims: To compare the sedoanalgesic effects of dexmedetomidine alone or with combination of ketamine. Material and Methods: After getting ethical approval and informed patient consent, 60 adult surgical patients, were randomly divided into two groups. Group KD (n = 30); received dexmedotomidine 0.5 µg/kg/h mixed with ketamine 0.5 µg/kg/h and Group DEX (n = 30); received dexmedotomidine at 0.5 mg/kg/h infusion only. In both the groups, study drugs were titrated (dexmedetomidine- 0.2-0.7 µg/kg/h and ketamine 0.2-0.7 mg/kg/h) to achieve target sedation. Hemodynamic variables, pain scores, sedation scores, and patient satisfaction were recorded. Qualitative and Quantitative data were analyzed with Pearson Chi-squared test and analysis of variance test, respectively. All analyses were done by using statistical package for social sciences (SPSS) version 16.0. Results: Pain scores were higher in group DEX than in group KD at 2 h and 4 h which was statistically significant (P < 0.05). At the end of 2 h, sedation scores were higher in group KD than in group DEX and was statistically significant (P < 0.05). Length of intensive care unit stay was almost comparable in both groups, and the time to tracheal extubation was lesser in ketamine-dexmedetomidine group as compared to the dexmedetomidine alone group. However the difference was statistically non-significant. Conclusions: By combining dexmedetomidine with ketamine we observed lower incidence of hypotension and bradycardia. Dexmedetomidine with ketamine combination therapy could be used safely and effectively as sedo-analgesic agent.

Protocolized Sedative Weaning vs Usual Care in Pediatric Critically Ill Patients: A Pilot Randomized Controlled Trial.

AIMS: The prolonged use of benzodiazepines and opioids can lead to an increase in the incidence of withdrawal syndrome. One of the known risk factors is the lack of a sedative-weaning protocol. This study established a sedative-weaning protocol and compared this protocol with the usual care of weaning in high-risk critically ill children. MATERIALS AND METHODS: This was an open-label, randomized controlled trial in a tertiary-care hospital. We recruited children aged 1 month to 18 years who had received intravenous sedative or analgesic drugs for at least 5 days. The exclusion criteria were patients who had already experienced the withdrawal syndrome. We established a weaning protocol. Eligible patients were randomly divided into the protocolized (intervention) and usual care (control) groups. The primary objective was to determine the prevalence of the withdrawal syndrome compared between two groups. RESULTS: Thirty eligible patients were enrolled (19 in the intervention and 11 in the control group). Baseline characteristics were not significantly different between both the groups. The prevalence of the withdrawal syndrome was 84% and 81% of patients in the intervention and control group, respectively. The duration of the initial weaning phase was shorter in the intervention group than in the control group (p value = 0.026). The cumulative dose of morphine solution for rescue therapy in the intervention group was statistically lower than that in the control group (p value = 0.016). CONCLUSION: The implementation of the sedative-weaning protocol led to a significant reduction in the percentage of withdrawal days and length of intensive care unit stay without any adverse drug reactions. External validation would be needed to validate this protocol. CLINICALTRIALSGOV IDENTIFIER: NCT03018977. HOW TO CITE THIS ARTICLE: Tiacharoen D, Lertbunrian R, Veawpanich J, Suppalarkbunlue N, Anantasit N. Protocolized Sedative Weaning vs Usual Care in Pediatric Critically Ill Patients: A Pilot Randomized Controlled Trial. Indian J Crit Care Med 2020;24(6):451-458.

Technology III: in-line vaporizer with reflector.

As the clinical advantages of vapor anesthesia (VA) for sedation of patients in ICU become more apparent, the ergonomics, economy and safety issues need to be better addressed. Here we describe the use of a new commercial digital in-line anesthetic vaporizer that can be attached to the inspiratory limb of a ventilator. If used with a simple, and easily assembled secondary circuit and anesthetic reflector, the circuit remains remote from the patient, the VA consumption approaches a physical minimum, VA level is controlled and monitored, and the tidal volume size is not limited.

A multinational, drug utilization study to investigate the use of dexmedetomidine (Dexdor®) in clinical practice in the EU.

AIMS: Dexmedetomidine (dexdor®) is approved in the European Union (EU) for sedation of adults in the intensive care unit (ICU). The present observational, retrospective study was requested by the European Medicines Agency to investigate dexmedetomidine use in clinical practice, with a particular focus on off-label use, including the paediatric population. METHODS: Study countries and sites were chosen from those with highest dexmedetomidine use, based on sales. Site selection (blind) was conducted by a multispecialist, independent group. Anonymized data on demographics, treatment indication, dexmedetomidine dosing, concomitant medications and treatment effectiveness were collected retrospectively from records of all dexmedetomidine-treated patients at the site during the enrolment period. Informed consent was waived, to avoid influencing the prescribing of dexmedetomidine. Recruitment was completed within 18 months of first site initiation. RESULTS: Data from 2000 patients were collected from 16 hospitals in four EU countries (Finland 750, Poland 505, Germany 470, Austria 275). The median age was 62 years, with more males (70.2%) than females. Dexmedetomidine was primarily used in the adult ICU (86.0%) for ICU sedation (78.6%) and mostly dosed according the product label. The intended sedative effect was obtained in 84.9% of administrations. Paediatric use (5.9% of patients, mostly in Austria and Finland) occurred mainly in the adult or paediatric ICU (75.6%) for sedation (67.2%). CONCLUSIONS: Overall, most patients were treated with dexmedetomidine according to the product labelling. Use in children was limited but significant and similar in scope to that in adults. Administrations not fully according to the product labelling usually occurred in an ICU environment and reflected extensively investigated clinical uses of dexmedetomidine.

[New technical developments for inhaled sedation]. / Neue technische Entwicklungen der inhalativen Sedierung.

The circle system has been in use for more than 100 years, whereas the first clinical application of an anaesthetic reflector was reported just 15 years ago. In the circle system, all breathing gas is rebreathed after carbon dioxide absorption. A reflector, on the other hand, with the breathing gas flowing to and fro, specifically retains the anaesthetic during expiration and resupplies it during the next inspiration. A high reflection efficiency (number of molecules resupplied/number of molecules exhaled, RE 80-90%) decreases consumption. In analogy to the fresh gas flow of a circle system, pulmonary clearance ((1-RE) × minute ventilation) defines the opposition between consumption and control of the concentration.It was not until reflection systems became available that volatile anaesthetics were used routinely in some intensive care units. Their advantages, such as easy handling, and better ventilatory capabilities of intensive care versus anaesthesia ventilators, were basic preconditions for this. Apart from AnaConDa™ (Sedana Medical, Uppsala, Sweden), the new MIRUS™ system (Pall Medical, Dreieich, Germany) represents a second, more sophisticated commercially available system.Organ protective effects, excellent control of sedation, and dose-dependent deep sedation while preserving spontaneous breathing with hardly any accumulation or induction of tolerance, make volatile anaesthetics an interesting alternative, especially for patients needing deep sedation or when intravenous drugs are no longer efficacious.But obviously, the outcome is most important. We know that deep intravenous sedation increases mortality, whereas inhalational sedation could prove beneficial. We now need prospective clinical trials examining mortality, but also the psychological outcome of those most critically ill patients sedated by inhalation or intravenously.

Clinical Decision Support and Closed-Loop Control for Cardiopulmonary Management and Intensive Care Unit Sedation Using Expert Systems.

Patients in the intensive care unit (ICU) who require mechanical ventilation due to acute respiratory failure also frequently require the administration of sedative agents. The need for sedation arises both from patient anxiety due to the loss of personal control and the unfamiliar and intrusive environment of the ICU, and also due to pain or other variants of noxious stimuli. While physicians select the agent(s) used for sedation and cardiovascular function, the actual administration of these agents is the responsibility of the nursing staff. If clinical decision support systems and closed-loop control systems could be developed for critical care monitoring and lifesaving interventions as well as the administration of sedation and cardiopulmonary management, the ICU nurse could be released from the intense monitoring of sedation, allowing her/him to focus on other critical tasks. One particularly attractive strategy is to utilize the knowledge and experience of skilled clinicians, capturing explicitly the rules expert clinicians use to decide on how to titrate drug doses depending on the level of sedation. In this paper, we extend the deterministic rule-based expert system for cardiopulmonary management and ICU sedation framework presented in [1] to a stochastic setting by using probability theory to quantify uncertainty and hence deal with more realistic clinical situations.

Washout and Awakening Times after Inhaled Sedation of Critically Ill Patients: Desflurane Versus Isoflurane.

In recent years, inhaled sedation has been increasingly used in the intensive care unit (ICU). The aim of this prospective, controlled trial was to compare washout and awakening times after long term sedation with desflurane and isoflurane both administered with the Mirus™ system (TIM GmbH, Koblenz, Germany). Twenty-one consecutive critically ill patients were alternately allocated to the two study groups, obtaining inhaled sedation with either desflurane or isoflurane. After 24 h study sedation, anesthetic washout curves were recorded, and a standardized wake-up test was performed. The primary outcome measure was the time required to decrease the endtidal concentration to 50% (T50%). Secondary outcome measures were T80% and awakening times (all extremities moved, RASS -2). Decrement times (min) (desflurane versus isoflurane, median (1st quartile-3rd quartile)) (T50%: 0.3 (0.3-0.4) vs. 1.3 (0.4-2.3), log-rank test P = 0.002; P80%: 2.5 (2-5.9) vs. 12.1 (5.1-20.2), P = 0.022) and awakening times (to RASS -2: 7.5 (5.5-8.8) vs. 41.0 (24.5-43.0), P = 0.007; all extremities moved: 5.0 (4.0-8.5) vs. 13.0 (8.0-41.25), P = 0.037) were significantly shorter after desflurane compared to isoflurane. The use of desflurane with the Mirus™ system significantly shortens the washout times and leads to faster awakening after sedation of critically ill patients.

Adult sedation and analgesia in a resource limited intensive care unit - A Systematic Review and evidence based guideline.

BACKGROUND: Sedation and analgesia are essential in the intensive care unit in order to promote control of pain, anxiety, prevent loss of materials, accidental extubation and improve the synchrony of patients with ventilator. However, excess of these medications leads to an increased morbidity and mortality, and thus demands protocol. METHODS: Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Protocol have been used to undertake this review. Pub Med, Cochrane Library, and Google Scholar search engines were used to find up-to-date evidence that helps to draw recommendations and conclusions. RESULTS: In this Guideline and Systematic Review, we have used 16 Systemic Review and Meta-Analysis, 3 Evidence-Based Guidelines and 10 RCT Meta-Analysis, 6 Systemic Reviews of Non-randomized Studies, 8 Randomized Clinical Trials, 11 Cohort Studies, 5 Cross-Sectional Studies and 1 Case Report with their respective study descriptions. DISCUSSION: Analgesia, which as a sedation basement can reduce sedative use, is key aspect of treatment in ICU patients, and we can also conclude that an analgesic sedation regimen can reduce the occurrence of delirium by reducing sedatives. The aim of this guideline and the systematic review is to write up and formulate analgesia-based sedation for limited resource settings. CONCLUSIONS: Analgesia and sedation are effective in critically ill patients; however, too much sedation is associated with longer periods of mechanical ventilation and longer duration of ICU stay. Poorly managed ICU patients have a delirium rate of up to 80%, increased mortality, longer hospital stays, higher hospital costs and bad long-term outcomes.

A Randomized Placebo-controlled Trial of Clonidine Impact on Sedation of Mechanically Ventilated ICU Patients.

Clonidine has sedative and analgesic properties. Randomized studies examining these properties in mechanically ventilated ICU patients are scarce. This study was designed to assess the impact of clonidine on sedative agent use in mechanically ventilated patients. In a prospective, randomized, double blind, placebo-controlled study in a general ICU of a university medical center in Tehran, Iran, 40 patients, over 18 years on mechanical ventilation for 3 days or more randomized into 2 equal groups of clonidine and placebo. Clonidine arm received usual sedation and enteral clonidine 0.1 mg TID and escalated to 0.2 mg TID on the second day if hemodynamics remained stable. Ramsay Sedation Score was used to assess sedation. Opioids and midazolam were used in all patients. 10 patients in clonidine and 3 in placebo arms had history of drug abuse (P = 0.018). The mean of sedatives used in the clonidine/placebo arms (mg/day) were; MED (Morphine Equivalent Dose) 91.4 ± 97.9/112.1 ± 98.8 P=0.39, midazolam 7.1 ± 7.9/8.3 ± 9.2 P=0.66 and propofol 535.8 ± 866.7/139.1 ± 359.9 P=0.125. After adjusting for addiction and propofol, clonidine reduced MED use by 79.6 mg/day (P=0.005) and midazolam by 5.41 mg/day (P = 0.05). Opioids and midazolam need reduced by clonidine co-administration regardless of history of drug abuse. Acceptable side effect profile and the lower cost of clonidine could make it an attractive adjunct to sedative agents in ICU.

A review of the practice of sedation with inhalational anaesthetics in the intensive care unit with the AnaConDa(®) device.

The intensive care unit (ICU) environment is often perceived to be hostile and frightening by patients due to unfamiliar surroundings coupled with presence of numerous personnel, monitors and other equipments as well as a loss of perception of time. Mechanical ventilation and multiple painful procedures that often need to be carried out in these critically ill patients add to their overall anxiety. Sedation is therefore required not only to allay the stress and anxiety, but also to allow for mechanical ventilation and other invasive therapeutic and diagnostic procedures to be performed. The conventional intravenous sedative agents used in ICUs suffer from problems of over sedation, tachyphylaxis, drug accumulation, organ specific elimination and often lead to patient agitation on withdrawal. All this tend to prolong the ventilatory as well as ICU and hospital discharge time, which increase the risk for infection and add to the overall increase in morbidity, mortality and hospital costs. In 2005, the anaesthetic conserving device (AnaConDa(®)) was marketed for ICU sedation with volatile anaesthetic agents. A number of trials have shown the effectiveness of using volatile anaesthetic agents for ICU sedation with the AnaConDa device. Compared with intravenous sedatives, use of volatile anaesthetic agents have resulted in shorter wake up and extubation time, lesser duration of mechanical ventilation and faster discharge from hospitals. This review shall focus on the benefits, technical pre-requisites and status of sedation with volatile anaesthetic agents in ICUs with the AnaConDa(®) device.