Propofol infusion Syndrome

Practice Problem: Pressure injuries (PIs) are a significant healthcare problem globally. Adult patients in the intensive care setting are especially vulnerable to the development of PIs given the acuity of their diagnoses requiring extensive treatments, procedures and the use of multiple medical devices. PICOT: The PICOT question that guided this project was, “In adult intensive care unit (ICU) patients, how does the effect of implementing a pressure injury prevention bundle compare in patients who received the bundle, and patients receiving standard pressure injury prevention in reducing the incidence of pressure injuries after two months?” Evidence: Evidence exist that bundle implementation significantly reduced incidence of PIs in adult ICU patients. Intervention: A pressure injury preventive bundle consisting of six evidence-based interventions were consistently and collectively implemented to reduce incidence of PIs in adult ICU patients at a tertiary hospital in South Texas. Further, a multidisciplinary approach, monitoring, auditing, and providing constructive feedback to staff were employed to ensure appropriate implementation and increase likelihood of achieving positive outcomes. Outcome: Findings revealed a 7.37% reduction in incidence after two months of bundle implementation. Also, findings showed more than 90% compliance with five out of the six components of the bundle. Conclusion: The reduction in the incidence of PIs with the implementation of a pressure injury preventive bundle in adult ICU patients was not statistically significant. However, the reduction indicated a clinically meaningful improvement in pressure injury outcomes two months after implementing the bundle.

The difficulty in achieving tight glycemic control (TGC)1,2 in the adult intensive care unit (ICU) is well documented.3,4 We aimed to explore the impact of insulin adsorption onto infusion sets in the laboratory and to assess retrospectively if higher insulin doses are required after syringe changes in practice in the ICU. Adsorption is reported to occur predominantly during the first hour of infusion, after which binding sites are saturated.5 There is greater insulin recovery with faster flow rates and higher insulin concentration.6 The clinical significance of such adsorption in the ICU setting is uncertain.5 In our study—approved by the local ethics committee—adsorption of insulin onto the giving sets used in our adult ICU was analyzed. The infusion set used was a 50 ml polypropylene syringe (BD Plastipak®) and 1.6 ml/200 cm polyethylene (PE) tubing (Cardinal Health, extension set). In the laboratory, the concentration investigated was 1 U/ml of neutral insulin in sodium chloride 0.9%. The concentrations were determined using a high-performance liquid chromatography method with a Jupitor 300, 5 μm C18, 250 mm × 4.6 mm column (Phenomenex), a mobile phase of 30% acetonitrile and 0.1% TFA in water, and ultraviolet detection at 210 nm. Significant insulin adsorption of 10% occurred during the first hour of an infusion when the infusion rate was 1 ml/h (Figure 1). Our experience suggests that this is a common infusion rate used in intensive insulin therapy. No significant adsorption occurred when the infusion rate was 4 ml/h, although a trend could be seen with solution leaving the PE tubing at the beginning of the time period having a lower insulin concentration, which increased with time. Figure 1. The mean (± standard error) insulin concentration versus time with an infusion rate of 1 U/h. The infusion rates used before and after an infusion set change were investigated for 17 ICU patients known to have been managed with a TGC protocol, aiming for glycemia of 4.4–6.1 mmol/liter, to examine any relationship between the duration of usage of the infusion set and the variation in insulin dosing required. These patients were not prescribed drugs known to affect glucose control, such as inotropes and corticosteroids. In the ICU patients, a significantly higher insulin infusion rate was required after an infusion set change when the infusion rate was 1 ml/h or lower. After an infusion set change, the rate was adjusted upward in 76.5% of cases. In conclusion, we found in the laboratory that less insulin is delivered during the first three hours after an infusion set change, when the infusion rate is 1 ml/h or lower, due to adsorption onto infusion sets. In the ICU, a higher infusion rate was frequently required after an infusion set change when the infusion rate was 1 ml/h or lower. Our results indicate that at low infusion rates, if the syringe and line are not primed, only 90% expected insulin is delivered. The clinical impact of a loss of 0.1 U/h of insulin is questionable, but in practice when syringes were changed, higher rates were frequently required. Further investigation should be undertaken to confirm these findings.

We are uncertain of the effects of information or education interventions given to adult ICU patients and their carers, as the evidence in all cases was of very low certainty, and our confidence in the evidence was limited. Ongoing studies may contribute more data and introduce more certainty when incorporated into future updates of the review.

The death of a loved one in the intensive care unit may cause prolonged grief, social distress, and even symptoms of posttraumatic stress in family members. End-of-life interventions, such as grief education materials, telephone follow-up, and cards, are an important part of bereavement care for families. However, use of these interventions varies across institutions, and research findings on their effectiveness are conflicting.Takaoka and colleagues examined the use of multiauthored, customized handwritten sympathy cards mailed to families 2 to 8 weeks post mortem. They interviewed family members and clinicians and identified 3 themes: The use of personalized, written condolences from staff was experienced as a meaningful and compassionate intervention for bereaved families.See Article, pp 422-428Pressure injuries occur twice as often in intensive care unit (ICU) patients as in other acute care patients, with estimated costs of care exceeding $26.8 billion in the United States. Although there are known risk factors for hospital-acquired pressure injury (HAPI), such as decreased mobility, having surgery, and age greater than 65 years, little research has examined the relationship between skin status and HAPI in ICU patients.Alderden and colleagues examined data from routine nursing skin assessments to identify risk factors for HAPI in adult surgical ICU patients. They found the following: Although further study is warranted to examine intraoperative risk factors, the authors recommend nurses consider the impact of skin changes on the development of HAPIs and remove causes of skin irritation.See Article, pp e128-e134Catheter-associated urinary tract infections continue to occur in both intensive care unit (ICU) patients and non-ICU patients, despite national prevention initiatives. Use of bladder scanning and ultrasound technology has helped to decrease the number of indwelling urinary catheter days, but the technology yields inaccuracies in patients with acute kidney injury, especially those with abdominal fluid/ascites.Schallom et al compared the accuracy of new bladder scanning technology and 2-dimensional ultrasound in measuring bladder volume in ICU patients unable to void 6 hours after catheter removal or patients receiving dialysis. They found Both bladder scanning and ultrasound can be used to measure bladder volumes accurately, but findings suggest that ultrasound should be used to measure bladder volume in patients with ascites.See Article, pp 458-467Many intensive care unit (ICU) patients require feeding tubes for nutritional support and medication delivery. Traditional practice includes every-4-hour assessment to verify tube placement. However, complications from malplaced feeding tubes continue to occur owing to inaccurate verification methods and lack of knowledge about tube migration.Using an electromagnetic placement device (EMPD) for tube placement, Bourgault and colleagues explored the factors associated with tube migration in adult ICU patients. They found See Article, pp 439-447

PROPOFOL is commonly used for intensive care unit sedation and prolonged procedures in the adult population where both deep sedation and quick emergence are required. Several recent reports have described a "propofol infusion syndrome," occurring in both pediatric1–7and adult2,8–10patients receiving prolonged high-dose infusions of propofol (> 75 μg · kg−1· min−1× > 24 h). The syndrome is characterized as a severe metabolic acidosis, sometimes associated with myocardial dysfunction, rhabdomyolysis, or death. Although some reports have documented high anion gap, lactic acidosis, others have documented only a metabolic acidosis without further characterization. All cases of propofol infusion syndrome reported thus far have occurred in critically ill patients receiving multiple other drugs, creating some controversy as to whether propofol alone was its cause.11–13We now report a case of metabolic acidosis, without ventilatory depression or hypoxia, in an otherwise healthy patient receiving propofol as the sole anesthetic agent during an ablation for atrial fibrillation. Approval for this case review was obtained from the institutional review board of the Mayo Clinic College of Medicine.A 31-yr-old woman (weight, 99.2 kg; height, 162 cm) with chronic atrial fibrillation was scheduled to undergo radiofrequency ablation for pulmonary vein isolation. She had a history of atrial fibrillation since the age of 22 yr and was minimally symptomatic, with no evidence of rate-related ventricular dysfunction or thromboembolic events. Except for occasional gastric reflux, she was otherwise healthy. She had reported "waking up early" during a previous anesthetic. Echocardiography showed normal ventricular function with a left ventricular ejection fraction of 55% and mild atrial enlargement. Medications were limited to 50 mg atenolol daily (stopped 4 days before ablation), 325 mg aspirin daily, and oral contraceptives. Preoperative laboratory results were unremarkable, including 11.5 g/dl hemoglobin, 0.9 mg/dl creatinine, 138 mEq/l Na+, and 4.9 mEq/l K+.The initial anesthetic plan was to use propofol as the sole sedative, based on its rapid metabolism and the clinical impression that propofol suppresses arrhythmogenic foci during radiofrequency ablation to a lesser extent than other available anesthetic agents. Monitoring included electrocardiography, pulse oximetry, continuous carbon dioxide monitoring of gas sampled at the nares, a femoral arterial catheter, and a urinary catheter. Because of the potential for respiratory depression with prolonged deep sedation in a nonintubated patient, arterial blood gas analyses were obtained intermittently during the procedure.Sedation was induced with 25 μg · kg−1· min−1propofol with supplemental oxygen by facemask at 4 l/min. The Diprivan® Injectable Emulsion formulation of propofol (AstraZeneca, Wilmington, DE) was used throughout, containing 10 mg/ml propofol and 0.005% disodium edetate. The exact vial sizes used were not recorded on the written anesthesia record. Based on our practice patterns at that time, the propofol infusion was almost certainly administered directly from a 100-ml infusion vial sterilely spiked with a solution administration set leading to an infusion pump. The source of supplemental boluses was not specified on the written record but would have been either from the 100-ml infusion vial already in use or from a 20-ml glass vial opened separately. Our practice is to discard unused propofol at the end of each case, so that vials would have been opened fresh for this case. The case reported was the first case of the day, and vials would have been open no longer than 1 h before the case. Lot numbers and expiration dates for the vials of propofol used could not be identified on retrospective inspection.The rate of propofol infusion was quickly increased to assist with patient immobility and ranged from 50 to 125 μg · kg−1· min−1throughout the procedure, together with intermittent boluses. The course of propofol therapy and arterial blood gases during the procedure is shown in figure 1. The average rate at which propofol was administered was 83 μg · kg−1· min−1, over a period of 395 min. An acidosis progressively developed, which was entirely metabolic. Pulse oximetry documented oxygen saturation (Spo2) greater than 95% at all times, and arterial oxygen tension (Pao2) and arterial carbon dioxide tension (Paco2) showed no evidence of hypoxia or respiratory depression on any arterial blood gas. There was no prolonged hypotension, and the average urine output was 250 ml/h throughout the procedure. Blood loss was minimal. The only other drug therapies used while propofol was administered were heparin, cefazolin, and 2 mg midazolam given as 1 mg at 51 min and 2 × 0.5 mg at 180 min after the start of anesthesia. Na+and K+at 51 and 194 min were 142 and 4.2 mEq/l and 142 and 4.0 mEq/l, respectively.At 395 min, the pH was 7.30, and base excess was −8. Because of patient restlessness and movement despite heavy sedation, intermittent airway obstruction requiring manual positioning to correct, and concern about an evolving metabolic acidosis with high-dose propofol, the patient was intubated and mechanically ventilated. The propofol infusion was discontinued, and no further propofol boluses were given. Total intravenous fluid to this point was between 2 and 3 l saline, 0.9%. A fentanyl infusion at 17–34 ng · kg−1· min−1with 75% N2O was begun and continued for the rest of the procedure. Sodium bicarbonate 15 mEq was given at 475 min, but the largest change in pH and base excess toward normal occurred between discontinuation of propofol at 395 min and the blood gas sampled at 433 min. By 560 min, the metabolic acidosis had partially resolved. At the end of the procedure at 720 min, the trachea was extubated without complications. Total intravenous fluid during the procedure was 5.85 l saline, 0.9%. No further arterial blood gas analyses were obtained on the day of the procedure. After the procedure, the patient had normal physical examination results and no complaints. Laboratory values obtained 2–4 days after the procedure were unremarkable: Na+, 137–139 mEq/l; K+, 3.5–3.9 mEq/l; Cl−103–106 mEq/l; venous HCO3−25–26 mEq/l; anion gap, 8.We report the development of significant, reversible, metabolic acidosis without ventilatory depression or hypoxia in a healthy patient receiving high-dose propofol and no other drugs likely to cause metabolic acidosis. The mechanism for this mild probable propofol infusion syndrome remains unclear. There was no evidence of renal failure causing decreased excretion of endogenous acids or increased loss of bicarbonate. Moreover, venous bicarbonate, creatinine, and anion gap values obtained after the procedure were normal, showing the absence of underlying chronic renal disease.Increased lactic acid production caused by low cardiac output or a regional steal syndrome must be considered because propofol is both a cardiac depressant and vasoactive,14and cardiac failure has been reported with the propofol infusion syndrome.1,2However, cardiac failure with propofol is usually a late, fatal development after metabolic acidosis, rather than an early cause of metabolic acidosis. This patient's hemodynamics, urine output, and stable renal status argue against cardiovascular failure as the proximate cause of her metabolic acidosis.Another potential cause of this patient's metabolic acidosis is impaired hepatic lactate metabolism. In several cases of propofol infusion syndrome, the development of a fatty or enlarged liver has been reported, and a case of isolated severe hepatotoxicity associated with propofol has also been reported.15The patient reported here did not have liver function laboratory tests, but she had no clinical evidence of hepatic disease before or after the procedure.There is both in vitro 16and clinical7evidence that high doses of propofol can inhibit mitochondrial respiration, which could cause metabolic acidosis. The glucuronide and sulfate products of phase II propofol metabolism are unlikely to be toxic, but the intermediate dihydroxylated products are poorly characterized and potentially interconvertible to toxic quinones. Propofol quinone has been synthesized, and preliminary evidence has been presented of its mitochondrial toxicity.17Both a direct and a metabolite mitochondrial toxicity of propofol would be consistent with the idiosyncratic appearance of the propofol infusion syndrome, requiring both a sustained, high-dose infusion and as yet undetermined genetic variants of propofol clearance and metabolism.Sepsis can lead to metabolic acidosis and could occur with contaminated propofol because its lipid emulsion is a good culture medium.18Here, the lack of fever and sustained hypotension and the uneventful postoperative recovery argue against sepsis in this patient. No exogenous acid load was administered to this patient; she received only the Diprivan® formulation of propofol (pH 7.5–8.0), rather than a generic formulation (pH 4.5–6.4; Baxter Healthcare Corporation, New Providence, NJ).Rapid administration of large volumes of 0.9% intravenous saline can cause dilutional acidosis.19,20Unfortunately, the concentration of serum chloride, which would have clarified the contribution of saline administration to this patient's acidosis, was not determined during the acidosis. However, comparison to published studies of dilutional acidosis suggests that 0.9% saline is unlikely to account for all of this patient's acidosis. In adult gynecologic surgery patients receiving 6 l saline, 0.9%, over 2 h, base excess decreased to −6.7 mm by 2 h.20Such dilutional changes require rapid administration of volumes beyond the ability of native homeostatic mechanisms to compensate.19At the time of intubation, our patient had received at most 3 l saline, 0.9%, over 6.5 h, with a base excess of −8. Hence, compared with that study,20our patient had a more negative base excess despite receiving half the saline volume over more than triple the time period, with more time for urinary response to a putative dilutional acidosis. Furthermore, her acidosis improved after the propofol was stopped, although she received a similar volume (at least 2.85 l) of 0.9% saline over the final 5.5 h of the anesthetic.In conclusion, the case reported here is significant because it is the first documented example of propofol potentially causing metabolic acidosis in the absence of any other drug likely to cause acidosis and without any other reasonable causative factors. It suggests that propofol infusion syndrome is in fact due to propofol or a propofol metabolite, is reversible in its early stages, and is consistent with previous cautions to avoid high-dose, prolonged infusions of propofol.1,2It also illustrates the utility of monitoring arterial blood gases in cases where the advantages of propofol infusion greater than 75 μg · kg−1· min−1for more than a few hours seem to outweigh its risks.

The objective of this scoping review was to explore existing literature on protocols initiated by nurses for a spontaneous breathing trial in adult intensive care unit (ICU) patients in order to examine and conceptually map the evidence, and identify gaps in the literature. Nurses are vital in the care of the critically ill mechanically ventilated patient. By involving the nurse in the weaning process through implementing the final stage of the weaning process, the spontaneous breathing trial, patients may liberate from mechanical ventilation more readily, thereby reducing the cost of care and number of complications associated with prolonged ventilation. This review considered experimental and quasi-experimental study designs, analytical observational studies, case-control studies, analytical cross-sectional studies, descriptive observational studies, qualitative studies, and text and opinion papers. Adult ICU patients, aged 18 and over who were mechanically ventilated and candidates for weaning to spontaneous breathing trials, were included in the review. Adult ICUs included but were not limited to burn ICUs, cardiovascular ICUs, medical ICUs, neurological ICUs, surgical ICUs and trauma ICUs in all geographic locations. This scoping review considered studies that examined the use of nurse-initiated protocols for a spontaneous breathing trial. The Joanna Briggs Institute scoping review methodology was used. Key information sources searched were Cochrane Database of Systematic Reviews, PubMed, PROSPERO, DARE, CINAHL, Embase, Scopus, Academic Search Premier, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, MedNar, ProQuest Dissertations and Theses, Papers First and societal websites with information relevant to the scoping review. Only studies published in English were included, and no date limits were applied. The data extraction tool was developed by the authors to examine information retrieved from the studies. Four studies, with 430 participants, were included in this review. One study was a non-randomized controlled trial, two were randomized controlled studies, and one was a text and opinion paper. The four studies included in the review identified both eligibility criteria for spontaneous breathing trial initiation, detailed elements of a spontaneous breathing trial, and criteria for success. Three of the four studies reported outcomes with the use of protocols for spontaneous breathing trials initiated by nurses. All included studies support the utilization of protocols and allowing the nurse to initiate the protocol, however variations in the eligibility criteria, details of the spontaneous breathing trial and success criteria create ambiguity in practice.

The utility of procalcitonin to manage patients with infections is unclear. A systematic review of comparative studies using procalcitonin-guided antibiotic therapy in patients with infections was performed. Randomized, controlled trials comparing procalcitonin-guided initiation, intensification, or discontinuation of antibiotic therapy to clinically guided therapy were included. Outcomes were antibiotic usage, morbidity, and mortality. MEDLINE, EMBASE, the Cochrane Database, National Institute for Clinical Excellence, the National Guideline Clearinghouse, and the Health Technology Assessment Programme were searched from January 1, 1990 to December 16, 2011. Eighteen randomized, controlled trials were included. Data were pooled into clinically similar patient populations. In adult intensive care unit (ICU) patients, procalcitonin-guided discontinuation of antibiotics reduced antibiotic duration by 2.05 days (95% confidence interval [CI]: -2.59 to -1.52) without increasing morbidity or mortality. In contrast, procalcitonin-guided intensification of antibiotics in adult ICU patients increased antibiotic usage and morbidity. In adult patients with respiratory tract infections, procalcitonin guidance significantly reduced antibiotic duration by 2.35 days (95% CI: -4.38 to -0.33), antibiotic prescription rate by 22% (95% CI: -41% to -4%), and total antibiotic exposure without affecting morbidity or mortality. A single, good quality study of neonates with suspected sepsis demonstrated reduced antibiotic duration by 22.4 hours (P = 0.012) and reduced the proportion of neonates on antibiotics for ≥ 72 hours by 27% (P = 0.002) with procalcitonin guidance. Procalcitonin guidance can safely reduce antibiotic usage when used to discontinue antibiotic therapy in adult ICU patients and when used to initiate or discontinue antibiotics in adult patients with respiratory tract infections.

Sepsis is a dysregulated systemic response to infection that causes organ dysfunction. It is the leading cause of in-hospital mortality and is responsible for the longest, most expensive, hospital stays in the United States. Prognostic modeling of sepsis has demonstrated potential for improving treatment and outcomes for critical care patients. However, the majority of previous models have relied on an outdated definition of sepsis based on systemic inflammatory response syndrome (SIRS). Therefore, this study sought to build predictive models of sepsis using the most recent definition of sepsis, Sepsis-3. A total of three classification methods, including logistic regression (LR), support vector machines (SVM), and logistic model trees (LMT), were used to predict onset of sepsis in adult Intensive Care Unit (ICU) patients using vital signs and blood culture results. For patients who did not develop sepsis, predictor values were selected from a random 48-hour time window during the patient's ICU stay. For those who developed sepsis, a random time was selected for the patient within 48 to 6 hours prior to onset of sepsis, and the predictor values with the closest preceding time were extracted. The LMT produced superior classification performance compared with the LR and SVM. The wide time window used for data extraction improves the clinical utility of the models relative to those built in previous work. However, while the models showed similar sensitivity and specificity to previous models using the Sepsis-3 definition, they each showed a high false positive rate.

Electrocardiographic changes predicting sudden death in propofol-related infusion syndrome

Plasma neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in adult critically ill patients: A prospective study

A valid pain assessment is the foundation of adequate pain management. Pain assessment can be challenging, especially in adult intensive care unit (ICU) patients who are unable to self-report. In such situations, relying on observational assessment tools is an alternative strategy. This review describes and analyzes the development and psychometric properties of pain assessment tools developed for use with nonverbal critically ill adults. A total of 32 relevant papers that described the psychometric properties of eight pain assessment tools were included. The scale development process, psychometric properties (i.e., reliability and validity), and feasibility of pain assessment tools were analyzed using a 0 to 20 scoring system. Each pain assessment tool was scored independently by two reviewers. Of the eight behavioral pain scales developed for use in adult ICU patients, the Behavioral Pain Scale (BPS) and the Critical-Care Pain Observation Tool (CPOT) are considered to be the most valid and reliable for this purpose, according to the available evidence. Behavioral pain scales may be viable alternatives to assessing pain in ICU patients who are unable to self-report, but only valid, reliable, and feasible scales should be used for this purpose.

Since the introduction of propofol in 1977, it has been widely used for the induction and maintenance of anaesthesia and for sedation on the intensive care unit. Recently, case reports of suspected propofol infusion syndrome (PRIS) following short term infusions have been published. We set out to obtain a picture of the current use of propofol infusions by paediatric anaesthetists in Great Britain and Ireland. A questionnaire concerning the use of propofol infusions was sent to 388 paediatric anaesthetists. A total of 242 (62%) replies were received. 26% of anaesthetists used propofol infusions with at least a monthly frequency. 136 (56%) anaesthetists thought that propofol infusions were of benefit in reducing postoperative nausea and vomiting. The majority of anaesthetists did not state a maximum infusion rate or length of infusion. Of those anaesthetists who answered the questions the maximum rate used was 30 mg x kg(-1) x h(-1) and the longest time considered for an infusion was 72 h. Only 5 (2%) anaesthetists regularly used BIS monitoring, although 106 (44%) expressed a desire to use it if it was freely available in their hospitals. Modifications to infusions from 1% to 2% propofol were used by 38 (16%) anaesthetists and 28 (12%) used glucose infusions intra-operatively. There is a wide variety in the use of propofol infusions by paediatric anaesthetists. The mechanisms underlying PRIS are poorly understood and require further work to ensure propofol infusions are used appropriately for anaesthesia in children.

Reversible Lactic Acidosis and Electrocardiographic Changes in a Neurosurgical Patient During Propofol Anesthesia

We revised and expanded the “2010 Guideline for the Use of Sedatives and Analgesics in the Adult Intensive Care Unit (ICU).” We revised the 2010 Guideline based mainly on the 2018 “Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) in Adult Patients in the ICU,” which was an updated 2013 pain, agitation, and delirium guideline with the inclusion of two additional topics (rehabilitation/mobility and sleep). Since it was not possible to hold face-to-face meetings of panels due to the coronavirus disease 2019 (COVID-19) pandemic, all discussions took place via virtual conference platforms and e-mail with the participation of all panelists. All authors drafted the recommendations, and all panelists discussed and revised the recommendations several times. The quality of evidence for each recommendation was classified as high (level A), moderate (level B), or low/very low (level C), and all panelists voted on the quality level of each recommendation. The participating panelists had no conflicts of interest on related topics. The development of this guideline was independent of any industry funding. The Pain, Agitation/Sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep Disturbance panels issued 42 recommendations (level A, 6; level B, 18; and level C, 18). The 2021 clinical practice guideline provides up-to-date information on how to prevent and manage pain, agitation/sedation, delirium, immobility, and sleep disturbance in adult ICU patients. We believe that these guidelines can provide an integrated method for clinicians to manage PADIS in adult ICU patients.

Feasibility and inter-rater reliability of the ICU Mobility Scale