Associate Professor - Med Center Line, Anesthesiology, Perioperative and Pain Medicine
Director, Critical Care Core Clerkship, Stanford University School of Medicine (2005 - Present)
1) Implementation of the ICU Pain, Agitation, and Delirium Clinical Practice Guidelines;
2) ICU Outcomes Research: glycemic control, sedation scoring, ICU device related infections, database analysis;
3) Clinical Pharmacology (i.e., pharmacokinetics, pharmacodynamics) of sedatives (eg, midazolam, lorazepam, propofol, dexemedetomidine) administered to ICU patients.
Pain, agitation, and delirium (PAD) are common in critically ill patients. Consequently, analgesic and sedative medications are frequently administered to critically ill patients to treat PAD, to improve synchrony with mechanical ventilation, and to decrease the physiological stress response. However, prolonged, continuous deep sedation of intensive care unit (ICU) patients is associated with numerous adverse outcomes, including longer durations of mechanical ventilation, prolonged ICU stays, acute brain dysfunction, and an increased risk of death. The 2013 ICU PAD Guidelines were developed to provide a clear, evidence-based road map for clinicians to better manage PAD in critically ill patients. Significant knowledge gaps in these areas still remain, but if widely adopted, the PAD Guidelines can help bridge these gaps and will be transformative in terms of their impact on ICU care. Strong evidence indicates that linking PAD management strategies with ventilator weaning, early mobility, and sleep hygiene in ICU patients will result in significant synergistic benefits to patient care and reductions in costs. An interdisciplinary team-based approach, using proven process improvement strategies, and ICU patient and family activation and engagement, will help ensure successful implementation of the ICU PAD Care Bundle in ICUs. This paper highlights the major recommendations of the 2013 ICU PAD Guidelines. We hope this review will help ICU physicians and other health care providers advance the management of PAD in critically ill patients, and improve patients' clinical outcomes.
View details for Web of Science ID 000332946800005
View details for PubMedID 24424616
In 2006, the American College of Critical Care Medicine assembled a 20-member task force to revise the 2002 guidelines for sedation and analgesia in critically ill adults. This article describes the methodological approach used to develop the American College of Critical Care Medicine's 2013 ICU Pain, Agitation, and Delirium Clinical Practice Guidelines.Review article.Multispecialty critical care units.Adult ICU patients.The task force was divided into four subcommittees, focusing on pain, sedation, delirium, and related outcomes. Unique aspects of this approach included the use of: 1) the Grading of Recommendations Assessment, Development and Evaluation method to evaluate the literature; 2) a librarian to conduct literature searches and to create and maintain the pain, agitation, and delirium database; 3) creation of a single web-based database; 4) rigorous psychometric analyses of pain, sedation, and delirium assessment tools; 5) the use of anonymous electronic polling; and 6) creation of an ICU pain, agitation, and delirium care bundle.The pain, agitation, and delirium database includes over 19,000 references. With the help of psychometric experts, members developed a scoring system and analyzed the psychometric properties of 6 behavioral pain scales, 10 sedation/agitation scales, and 5 delirium monitoring tools. A meta-analysis was performed to assess the overall impact of benzodiazepine versus nonbenzodiazepine sedation on ICU outcomes. The pain, agitation, and delirium guidelines include 54 evidence-based statements and recommendations. The quality of evidence and strength for each statement and recommendation was ranked. In the absence of sufficient evidence or group consensus, no recommendations were made. An ICU pain, agitation, and delirium care bundle was created to facilitate adoption of the pain, agitation, and delirium guidelines. It focuses on taking an integrated approach to assessing, treating, and preventing pain, agitation/sedation, and delirium in critically ill patients, and it links pain, agitation, and delirium management to spontaneous awakening trials, spontaneous breathing trials, and ICU early mobility and sleep hygiene programs in order to achieve synergistic benefits to ICU patient outcomes.The 2013 ICU pain, agitation, and delirium guidelines provide critical care providers with an evidence-based, integrated, and interdisciplinary approach to managing pain, agitation/sedation, and delirium. The methodological approach used to develop the guidelines ensures that they are rigorous, evidence-based, and transparent. Implementation of the ICU pain, agitation, and delirium care bundle is expected to have a significant beneficial impact on ICU outcomes and costs.
View details for DOI 10.1097/CCM.0b013e3182a167d7
View details for Web of Science ID 000331152200001
View details for PubMedID 23989088
In 2013, the American College of Critical Care Medicine published a revised version of the pain, agitation, and delirium guidelines. The guidelines included an ICU pain, agitation, and delirium care bundle designed to facilitate implementation of the pain, agitation, and delirium guidelines.Review article.Multispecialty critical care units.Adult ICU patients.This article describes: 1) the ICU pain, agitation, and delirium care bundle in more detail, linking pain, sedation/agitation, and delirium management in an integrated and interdisciplinary fashion; 2) pain, agitation, and delirium implementation strategies; and 3) the potential synergistic benefits of linking pain, agitation, and delirium management strategies to other evidence-based ICU practices, including spontaneous breathing trials, ICU early mobility programs, and ICU sleep hygiene programs, in order to improve ICU patient outcomes and to reduce costs of care.Linking the ICU pain, agitation, and delirium management strategies with spontaneous awakening trials, spontaneous breathing trials, and early mobility and sleep hygiene programs is associated with significant improvements in ICU patient outcomes and reductions in their costs of care.The 2013 ICU pain, agitation, and delirium guidelines provide critical care providers with an evidence-based, integrated, and interdisciplinary approach to managing pain, agitation/sedation, and delirium. The ICU pain, agitation, and delirium care bundle provides a framework for facilitating implementation of the pain, agitation, and delirium guidelines. Widespread implementation of the ICU pain, agitation, and delirium care bundle is likely to result in large-scale improvements in ICU patient outcomes and significant reductions in costs.
View details for DOI 10.1097/CCM.0b013e3182a16ff0
View details for Web of Science ID 000331152200009
View details for PubMedID 23989099
To describe and analyze the development and psychometric properties of subjective sedation scales developed for critically ill adult patients.PubMed, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, ISI Web of Science, and the International Pharmaceutical Abstracts.English-only publications through December 2012 with at least 30 patients older than 18 years, which included the key words of adult, critically ill, subjective sedation scale, sedation scale, validity, and reliability.Two independent reviewers evaluated the psychometric properties using a standardized sedation scale psychometric scoring system.Among the 19,000+ citations extracted for the 2013 Society of Critical Care Medicine's Clinical Practice Guidelines for the Management of Pain, Agitation and Delirium and from December 2010 to 2012, 36 articles were identified compassing 11 sedation scales. The scale development process, psychometric properties, feasibility, and implementation of sedation scales were analyzed using a 0-20 scoring system. Two scales demonstrated scores indicating "very good" published psychometric properties: Richmond Agitation-Sedation Scale (19.5) and the Sedation-Agitation Scale (19). Scores with "moderate" properties include the Vancouver Interaction and Calmness Scale (14.3), Adaptation to the Intensive Care Environment (13.7), Ramsay Sedation Scale (13.2), Minnesota Sedation Assessment Tool (13), and the Nursing Instrument for the Communication of Sedation (12.8). Scales with "low" properties included the Motor Activity Assessment Scale (11.5) and the Sedation Intensive Care Score (10.5). The New Sheffield Sedation Scale (8.5) and the Observer's Assessment of Alertness/Sedation Scale (3.7) demonstrated "very low" published properties.Based on the current literature, and using a predetermined psychometric scoring system, the Richmond Agitation-Sedation Scale and the Sedation-Agitation Scale are the most valid and reliable subjective sedation scales for use in critically ill adult patients.
View details for DOI 10.1097/CCM.0b013e3182a16879
View details for Web of Science ID 000331152200002
View details for PubMedID 23989092
This pilot study was designed to identify which contextual factors facilitate/hinder the implementation of the awakening, breathing, coordination, delirium, and early mobility (ABCDE) bundle for guidance in future studies.The sources of data for this study included document review, planned site visits (including interviews and observations), a brief online contextual factors survey, and self-reported process and outcome data.All patients in the four participating SF Bay Area ICUs were eligible to be included in this pilot study.This study took place in the four San Francisco Bay Area ICUs participating in the ICU Clinical Impact Interest Group, funded by the Gordon and Betty Moore Foundation from January 2012 through June 2013.This was a pilot evaluation study to identify factors that facilitated/hindered the implementation of the ABCDE bundle, interventions designed to decrease the prevalence of ICU-acquired delirium and muscle weakness. The ABCDE bundle consists of spontaneous awakening trials, spontaneous breathing trials, coordination of awakening and breathing trials, choice of sedation, delirium screening and treatment, and early progressive mobility.Process data related to bundle element compliance were collected at baseline and monthly during the intervention period. Outcome data (average ICU length of stay and average days on mechanical ventilation) were collected at baseline and quarterly during the intervention period. Hospital-specific results of the online contextual factors survey and information gathered through interviews and observations during site visits also contributed to the analysis.Factors related to structural characteristics of the ICU, an organizational-wide patient safety culture, an ICU culture of quality improvement, implementation planning, training/support, and prompts/documentation are believed to have facilitated the rate and success of ABCDE bundle implementation. Excessive turnover (both in project and ICU leadership), staff morale issues, lack of respect among disciplines, knowledge deficits, and excessive use of registry staff are believed to have hindered implementation.Successful implementation of the elements of the ABCDE bundle can result in significant improvements in ICU patient care. The results of this study highlight specific structural and cultural elements of ICUs and hospitals that can positively and negatively influence the implementation of complex care bundles like the ABCDE bundle. Further research is needed to assess the influence of these contextual factors across a broader variety of ICUs and hospitals.
View details for DOI 10.1097/CCM.0b013e3182a2c2b1
View details for Web of Science ID 000331152200011
View details for PubMedID 23989090
Use of dexmedetomidine or propofol rather than a benzodiazepine sedation strategy may improve ICU outcomes. We reviewed randomized trials comparing a benzodiazepine and nonbenzodiazepine regimen in mechanically ventilated adult ICU patients to determine if differences exist between these sedation strategies with respect to ICU length of stay, time on the ventilator, delirium prevalence, and short-term mortality.We searched CINAHL, MEDLINE, the Cochrane databases, and the American College of Critical Care Medicine's Pain, Agitation, Delirium Management Guidelines' literature database from 1996 to 2013. Citations were screened for randomized trials that enrolled critically ill, mechanically ventilated adults comparing an IV benzodiazepine-based to a nonbenzodiazepine-based sedative regimen and reported duration of ICU length of stay, duration of mechanical ventilation, delirium prevalence, and/or short-term mortality. Trial characteristics and results were abstracted in duplicate and independently, and the Cochrane risk of bias tool was used for quality assessment. We performed random effects model meta-analyses where possible.We included six trials enrolling 1,235 patients: midazolam versus dexmedetomidine (n = 3), lorazepam versus dexmedetomidine (n = 1), midazolam versus propofol (n = 1), and lorazepam versus propofol (n = 1). Compared to a benzodiazepine sedative strategy, a nonbenzodiazepine sedative strategy was associated with a shorter ICU length of stay (n = 6 studies; difference = 1.62 d; 95% CI, 0.68-2.55; I = 0%; p = 0.0007) and duration of mechanical ventilation (n = 4 studies; difference = 1.9 d; 95% CI, 1.70-2.09; I2 = 0%; p < 0.00001) but a similar prevalence of delirium (n = 2; risk ratio = 0.83; 95% CI, 0.61-1.11; I2 = 84%; p = 0.19) and short-term mortality rate (n = 4; risk ratio = 0.98; 95% CI, 0.76-1.27; I2 = 30%; p = 0.88).Current controlled data suggest that use of a dexmedetomidine- or propofol-based sedation regimen rather than a benzodiazepine-based sedation regimen in critically ill adults may reduce ICU length of stay and duration of mechanical ventilation. Larger controlled studies are needed to further define the impact of nonbenzodiazepine sedative regimens on delirium and short-term mortality.
View details for DOI 10.1097/CCM.0b013e3182a16898
View details for Web of Science ID 000331152200003
View details for PubMedID 23989093
This article evaluates the methodology used to develop the updated American College of Critical Care Medicine/Society of Critical Care Medicine Pain Agitation and Delirium (PAD) Guidelines in terms of (1) evaluating the role of a medical librarian in the guidelines development process; (2) summarizing the impressions of the guideline task force members on the use of Grades of Recommendation, Assessment, Development, and Evaluation and anonymous voting to develop guideline questions, statements, and recommendations; and (3) analyzing the impact of this approach to developing clinical practice guidelines on interrater reliability in evaluating evidence, statements, and recommendations.
View details for DOI 10.1055/s-0033-1342988
View details for Web of Science ID 000319498100011
View details for PubMedID 23716316
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.
View details for DOI 10.1055/s-0033-1342970
View details for Web of Science ID 000319498100002
View details for PubMedID 23716307
To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002.The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over 6 yr in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (http://www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (http://www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2), and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend ?" is used throughout. A weak recommendation, either for or against an intervention, indicated that the trade-off between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest ?" is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflict of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding.These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.
View details for DOI 10.1097/CCM.0b013e3182783b72
View details for Web of Science ID 000313150300029
View details for PubMedID 23269131
To revise the "Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult" published in Critical Care Medicine in 2002.The American College of Critical Care Medicine assembled a 20-person, multidisciplinary, multi-institutional task force with expertise in guideline development, pain, agitation and sedation, delirium management, and associated outcomes in adult critically ill patients. The task force, divided into four subcommittees, collaborated over six years in person, via teleconferences, and via electronic communication. Subcommittees were responsible for developing relevant clinical questions, using the Grading of Recommendations Assessment, Development and Evaluation method (www.gradeworkinggroup.org) to review, evaluate, and summarize the literature, and to develop clinical statements (descriptive) and recommendations (actionable). With the help of a professional librarian and Refworks database software, they developed a Web-based electronic database of over 19,000 references extracted from eight clinical search engines, related to pain and analgesia, agitation and sedation, delirium, and related clinical outcomes in adult ICU patients. The group also used psychometric analyses to evaluate and compare pain, agitation/sedation, and delirium assessment tools. All task force members were allowed to review the literature supporting each statement and recommendation and provided feedback to the subcommittees. Group consensus was achieved for all statements and recommendations using the nominal group technique and the modified Delphi method, with anonymous voting by all task force members using E-Survey (www.esurvey.com). All voting was completed in December 2010. Relevant studies published after this date and prior to publication of these guidelines were referenced in the text. The quality of evidence for each statement and recommendation was ranked as high (A), moderate (B), or low/very low (C). The strength of recommendations was ranked as strong (1) or weak (2) and either in favor of (+) or against (-) an intervention. A strong recommendation (either for or against) indicated that the intervention's desirable effects either clearly outweighed its undesirable effects (risks, burdens, and costs) or it did not. For all strong recommendations, the phrase "We recommend..." is used throughout. A weak recommendation, either for or against an intervention, indicated that the tradeoff between desirable and undesirable effects was less clear. For all weak recommendations, the phrase "We suggest..." is used throughout. In the absence of sufficient evidence, or when group consensus could not be achieved, no recommendation (0) was made. Consensus based on expert opinion was not used as a substitute for a lack of evidence. A consistent method for addressing potential conflicts of interest was followed if task force members were coauthors of related research. The development of this guideline was independent of any industry funding.These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.
View details for Web of Science ID 000315611400011
View details for PubMedID 23261901
Intensive care units are complex and dynamic clinical environments in which the delivery of appropriate and timely care to critically ill patients depends on the integrated and efficient actions of providers with specialized training. The use of realistic clinical simulator systems can help to facilitate and standardize the training of critical-care physicians, nurses, respiratory therapists, and pharmacists without having the training process jeopardize the well-being of patients. In this article, we review the current state of the art of patient simulator systems and their applications to critical-care medicine, and we offer some examples and recommendations on how to integrate simulator systems into critical-care training.
View details for PubMedID 17895484
To develop clinical practice guidelines for the support of the patient and family in the adult, pediatric, or neonatal patient-centered ICU.A multidisciplinary task force of experts in critical care practice was convened from the membership of the American College of Critical Care Medicine (ACCM) and the Society of Critical Care Medicine (SCCM) to include representation from adult, pediatric, and neonatal intensive care units.The task force members reviewed the published literature. The Cochrane library, Cinahl, and MedLine were queried for articles published between 1980 and 2003. Studies were scored according to Cochrane methodology. Where evidence did not exist or was of a low level, consensus was derived from expert opinion.The topic was divided into subheadings: decision making, family coping, staff stress related to family interactions, cultural support, spiritual/religious support, family visitation, family presence on rounds, family presence at resuscitation, family environment of care, and palliative care. Each section was led by one task force member. Each section draft was reviewed by the group and debated until consensus was achieved. The draft document was reviewed by a committee of the Board of Regents of the ACCM. After steering committee approval, the draft was approved by the SCCM Council and was again subjected to peer review by this journal.More than 300 related studies were reviewed. However, the level of evidence in most cases is at Cochrane level 4 or 5, indicating the need for further research. Forty-three recommendations are presented that include, but are not limited to, endorsement of a shared decision-making model, early and repeated care conferencing to reduce family stress and improve consistency in communication, honoring culturally appropriate requests for truth-telling and informed refusal, spiritual support, staff education and debriefing to minimize the impact of family interactions on staff health, family presence at both rounds and resuscitation, open flexible visitation, way-finding and family-friendly signage, and family support before, during, and after a death.
View details for DOI 10.1097/01.CCM.0000254067.14607.EB
View details for Web of Science ID 000243739100038
View details for PubMedID 17205007
Inadequate nutritional intake in critically ill patients can lead to complications resulting in increased mortality and healthcare costs. Several factors limit adequate nutritional intake in intensive care unit patients given enteral feedings.To examine the adequacy of enteral nutritional intake and the factors that affect its delivery in patients receiving mechanical ventilation.A prospective, descriptive design was used to study 60 patients receiving enteral feedings at target or goal rate. Energy requirements were determined for the entire sample by using the Harris-Benedict equation; energy requirements for a subset of 25 patients were also determined by using indirect calorimetry. Energy received via enteral feeding and reason and duration of interruptions in feedings were recorded for 3 consecutive days.Mean estimated energy requirements (8996 kJ, SD 1326 kJ) and mean energy intake received (5899 kJ, SD 3058 kJ) differed significantly (95% CI 3297-3787; P < .001). A total of 41 patients (68.3%) received less than 90% of their required energy intake, 18 (30.0%) received within +/-10%, and 1 (1.7%) received more than 110%. Episodes of diarrhea, emesis, large residual volumes, feeding tube replacements, and interruptions for procedures accounted for 70% of the variance in energy received (P<.001). Procedural interruptions alone accounted for 45% of the total variance. Estimated energy requirements determined via indirect calorimetry and mean energy received did not differ.Most critically ill patients receiving mechanical ventilation who are fed enterally do not receive their energy requirements, primarily because of frequent interruptions in enteral feedings.
View details for Web of Science ID 000228688100008
View details for PubMedID 15840896
The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections in patients admitted to the intensive care unit has dramatically increased in recent years, with an associated increase in morbidity and mortality and the costs of caring for patients with MRSA infections. Although indiscriminate and inappropriate use of antibiotics has contributed to this phenomenon, horizontal transmission of MRSA between patients and health care providers is the principal cause of this observed increase. This article discusses the pathogenesis, epidemiology, treatment, and prevention of MRSA infections in critically ill patients.
View details for PubMedID 15325711
To determine whether the implementation of a nutritional management protocol in the ICU leads to the increased use of enteral nutrition, earlier feeding, and improved clinical outcomes in patients.Prospective evaluation of critically ill patients before and after the introduction of an evidence-based guideline for providing nutritional support in the ICU.The medical-surgical ICUs of two teaching hospitals.Two hundred critically ill adult patients who remained npo > 48 h after their admission to the ICU. One hundred patients were enrolled into the preimplementation group, and 100 patients were enrolled in the postimplementation group.Implementation of an evidence-based ICU nutritional management protocol.Nutritional outcome measures included the number of patients who received enteral nutrition, the time to initiate nutritional support, and the percent caloric target administered on day 4 of nutritional support. Clinical outcomes included the duration of mechanical ventilation, ICU and in-hospital length of stay (LOS), and in-hospital mortality rates. Patients in the postimplementation group were fed more frequently via the enteral route (78% vs 68%, respectively; p = 0.08), and this difference was statistically significant after adjusting for severity of illness, baseline nutritional status, and other factors (odds ratio, 2.4; 95% confidence interval [CI], 1.2 to 5.0; p = 0.009). The time to feeding and the caloric intake on day 4 of nutritional support were not different between the groups. The mean (+/- SD) duration of mechanical ventilation was shorter in the postimplementation group (17.9 +/- 31.3 vs 11.2 +/- 19.5 days, respectively; p = 0.11), and this difference was statistically significant after adjusting for age, gender, severity of illness, type of admission, baseline nutritional status, and type of nutritional support (p = 0.03). There was no difference in ICU or hospital LOS between the two groups. The risk of death was 56% lower in patients who received enteral nutrition (hazard ratio, 0.44; 95% CI, 0.24 to 0.80; p = 0.007).An evidence-based nutritional management protocol increased the likelihood that ICU patients would receive enteral nutrition, and shortened their duration of mechanical ventilation. Enteral nutrition was associated with a reduced risk of death in those patients studied.
View details for Web of Science ID 000221793700042
View details for PubMedID 15078758
To describe the variation in clinical practice strategies for the treatment of suspected ventilator-associated pneumonia (VAP) in a population of critically ill patients, and to determine whether initial empiric treatment with certain antibiotics, monotherapy vs combination antibiotic therapy, or appropriate vs inappropriate antibiotic therapy is associated with survival, length of hospital stay, or days free of antibiotics.Prospective, observational cohort study.Medical-surgical ICUs of two university-affiliated tertiary medical centers.Between May 1, 1998, and August 1, 2000, we screened 7,030 ICU patients and identified 156 patients with clinically suspected VAP. Patients were followed up until death or discharge from the hospital.The mean age was 62 years, mean APACHE (acute physiology and chronic health evaluation) II score was 14, and mortality was 34%. Combination antibiotic therapy was used in 53% of patients. Piperacillin-tazobactam, fluoroquinolones, vancomycin, cephalosporins, and aminoglycosides were the most commonly employed antibiotics. Initial empiric antibiotics were deemed appropriate in 92% of patients. The predominant organisms isolated from respiratory secretions included Pseudomonas aeruginosa and Staphylococcus aureus. Patients had lower in-hospital mortality rates if their initial treatment regimen included an antipseudomonal penicillin plus beta-lactamase inhibitor (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.21 to 0.80; p = 0.009). There was also a strong trend toward reduced mortality rates in patients treated with aminoglycosides (HR, 0.43; 95% CI, 0.16 to 1.11; p = 0.08). Specific antibiotic therapy was not associated with length of hospital stay or days free of antibiotics. Outcomes were similar for patients treated with monotherapy vs combination therapy, and for patients who received initial appropriate vs inappropriate therapy.Patients with clinically suspected VAP who receive initial empiric therapy with antipseudomonal penicillins plus beta-lactamase inhibitors, and possibly aminoglycosides, have lower in-hospital mortality rates when compared with those who are not treated with these antibiotics. These agents should be considered for the initial empiric therapy of VAP.
View details for Web of Science ID 000181536500035
View details for PubMedID 12628886
The pharmacology of propofol infusions administered for long-term sedation of intensive care unit (ICU) patients has not been fully characterized. The aim of the study was to develop propofol dosing guidelines for ICU sedation based on an integrated pharmacokinetic-pharmacodynamic model of propofol infusions in ICU patients.With Institutional Review Board approval, 30 adult male medical and surgical ICU patients were given target-controlled infusions of propofol for sedation, adjusted to maintain a Ramsay sedation scale score of 2-5. Propofol administration in the first 20 subjects was based on a previously derived pharmacokinetic model for propofol. The last 10 subjects were given propofol based on a pharmacokinetic model derived from the first 20 subjects. Plasma propofol concentrations were measured, together with sedation score. Population pharmacokinetic and pharmacodynamic parameters were estimated by means of nonlinear regression analysis in the first 20 subjects, then prospectively tested in the last 10 subjects. An integrated pharmacokinetic-pharmacodynamic model was used to construct dosing regimens for light and deep sedation with propofol in ICU patients.The pharmacokinetics of propofol were described by a three-compartment model with lean body mass and fat body mass as covariates. The pharmacodynamics of propofol were described by a sigmoid model, relating the probability of sedation to plasma propofol concentration. The pharmacodynamic model for propofol predicted light and deep levels of sedation with 73% accuracy. Plasma propofol concentrations corresponding to the probability modes for sedation scores of 2, 3, 4, and 5 were 0.25, 0.6, 1.0, and 2.0 microg/ml. Predicted emergence times in a typical subject after 24 h, 72 h, 7 days, and 14 days of light sedation (sedation score = 3 --> 2) with propofol were 13, 34, 198, and 203 min, respectively. Corresponding emergence times from deep sedation (sedation score = 5 --> 2) with propofol were 25, 59, 71, and 74 h.Emergence time from sedation with propofol in ICU patients varies with the depth of sedation, the duration of sedation, and the patient's body habitus. Maintaining a light level of sedation ensures a rapid emergence from sedation with long-term propofol administration.
View details for Web of Science ID 000170237800007
View details for PubMedID 11506101
To compare the effects of propofol with and without disodium edetate (EDTA) on cation metabolism in intensive care unit (ICU) patients with renal insufficiency who received propofol or propofol plus EDTA (propofol EDTA) for sedation and mechanical ventilation.Double-blind, randomised, multicentre study.Medical and surgical ICUs from 5 hospitals. Patients: Thirty-nine ICU patients with acute and chronic renal impairment expected to require at least 24 hours of continuous sedation and respiratory failure necessitating mechanical ventilation.Propofol or propofol EDTA administered for sedation by continuous intravenous infusion.The depth of sedation, as measured by the Modified Ramsay Sedation Scale, was similar in the 2 groups, when adjusted for dosing differences. The amount of propofol required to maintain adequate sedation was decreased in both groups compared to propofol requirements in ICU patients with normal renal function. EDTA levels were elevated at baseline in both groups. In the propofol EDTA group, the EDTA levels increased further by 20 % but decreased to below baseline EDTA levels at 48 hours after sedation. In the propofol group, EDTA levels decreased during sedation and remained below baseline levels at 48 hours after sedation. Patients in both groups were hypocalcaemic and hyperphosphataemic at baseline with low levels of 1,25-dihydroxyvitamin D and elevated parathyroid hormone (PTH) levels. Other than a slight difference in ionised serum calcium levels at 4 h after the start of sedation, there were no significant differences observed in serum calcium levels between the two groups. There were no significant differences in 1,25-dihydroxyvitamin D or PTH levels over time between the two groups. There was no significant effect on renal function in either group.The results of this study suggest that adding EDTA to propofol does not adversely affect cation homeostasis or renal function when used for sedation of ICU patients with renal insufficiency. Although EDTA levels increased over time from baseline levels in patients with renal insufficiency who receive propofol EDTA, this increase does not appear to be clinically significant, and EDTA levels return to below baseline levels within 48 hours of discontinuing the propofol EDTA infusion. The efficacy of propofol with and without EDTA also appears comparable in these patients.
View details for Web of Science ID 000166278900007
View details for PubMedID 11310906
Midazolam is commonly used for short-term postoperative sedation of patients undergoing cardiac surgery. The purpose of this multicenter study was to characterize the pharmacokinetics and intersubject variability of midazolam in patients undergoing coronary artery bypass grafting.With institutional review board approval, 90 consenting patients undergoing coronary artery bypass grafting were enrolled at three study centers. All subjects received sufentanil and midazolam via target-controlled infusions. After operation, midazolam was titrated to maintain deep sedation for at least 2 h. It was then titrated downward to decrease sedation for a minimum of 4 h more and was discontinued before tracheal extubation. Arterial blood samples were taken throughout the study and were assayed for midazolam and 1-hydroxymidazolam. Midazolam population pharmacokinetic parameters were estimated using NONMEM. Cross-validation was used to estimate the performance of the model.The pharmacokinetics of midazolam were best described by a simple three-compartment mammillary model. Typical pharmacokinetic parameters were V1 = 32.2 l, V2 = 53 l, V3 = 245 l, Cl1 = 0.43 l/min, Cl2 = 0.56 l/min, and Cl3 = 0.39 l/min. The calculated elimination half-life was 15 h. The median absolute prediction error was 25%, with a bias of 1.4%. The performance in the cross-validation was similar. Midazolam metabolites were clinically insignificant in all patients.The intersubject variability and predictability of the three-compartment pharmacokinetic model are similar to those of other intravenous anesthetic drugs. This multicenter study did not confirm previous studies of exceptionally large variability of midazolam pharmacokinetics when used for sedation in intensive care settings.
View details for Web of Science ID 000077376100019
View details for PubMedID 9856717
View details for Web of Science ID 000074754300005
Patients in the ICU who require intubation and mechanical ventilation benefit from adequate sedation and analgesia. Traditionally, this has been achieved using benzodiazepines and opioids. Alternatively, propofol is being administered for sedation of patients in the ICU with increasing frequency. Propofol has a number of properties that make it a potentially superior choice for sedation of intubated ICU patients. The rapid onset and offset of sedation with propofol, even after prolonged administration, allow for greater control over the level of sedation and more rapid weaning from mechanical ventilation. In addition, long-term administration of propofol does not appear to be associated with the development of tolerance, addiction, or withdrawal following discontinuation. Propofol suppresses cellular oxygen consumption and carbon dioxide production without increasing anaerobic metabolism. This may be beneficial in patients with severe hypoxemia, hypercarbia, or myocardial ischemia. Finally, the use of propofol may reduce or eliminate the need for other medications in these patients such as muscle relaxants, antihypertensives, lipid nutritional supplements, and analgesics, thereby simplifying their medication regimens and reducing the overall cost of their care while in the ICU. Propofol can be administered to critically ill patients for sedation with a high degree of safety and efficacy. Propofol causes systemic vasodilatation which may result in unwanted hypotension, especially in patients who are already hemodynamically compromised. Propofol also causes ventilatory depression, so its use should be restricted in the ICU to patients whose airway is protected by an endotracheal tube and whose ventilation is closely monitored. Finally, continuous administration of propofol may cause clinically significant hypertriglyceridemia in patients with disordered triglyceride metabolism, or in patients receiving excessive doses of propofol or parenteral lipid supplements. Although propofol is more expensive than equipotent doses of other sedative agents, the additional cost of using propofol for sedation of critically ill patients in the ICU may be more than offset by the savings accrued from faster times to extubation, shorter ICU stays, and the use of fewer medications to manage these patients. Further research needs to be done to determine the potential clinical and cost benefits of using propofol for sedation of patients in the ICU.
View details for Web of Science ID A1995QX08000009
View details for PubMedID 7635554
View details for DOI 10.1111/j.1365-2125.1995.tb04557.x
The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. Such agents include metformin, phenformin, and buformin. The use of phenformin was discontinued in the United States in 1976 because of probable association with lactic acidosis. However, metformin is currently in common use in many parts of the world. In this report, we describe a patient with severe lactic acidosis secondary to metformin administration, and review the literature relevant to biguanide-associated lactic acidosis.We describe a diabetic man with end-stage renal failure and diabetes mellitus who was hospitalized with life-threatening lactic acidosis (lactate, 10.9 mmol/L). Unbeknownst to the hospital staff, he was being treated with metformin, which had been prescribed in Indonesia.Arterial blood gas analysis revealed a pH of 6.76 and a bicarbonate level of 1.6 mmol/L prior to treatment. Following therapy, which included oxygen, volume expansion, other supportive therapy, and hemodialysis, the patient completely recovered and was discharged from the hospital.Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency. We review the literature relevant to the pathogenesis and therapy of biguanide-associated lactic acidosis. Physicians who have completed their training after 1976 may not be familiar with metformin and other biguanides, but with the increasing numbers of immigrants to the United States, physicians should be aware of the potential complications of these medications.
View details for Web of Science ID A1992JX15100023
View details for PubMedID 1444694
Tricuspid valve stenosis in the setting of endocarditis is associated with a high morbidity. Diagnostic approaches incorporate a high clinical index of suspicion, echocardiographic evidence, and inferences about hemodynamic data derived from pulmonary artery catheterization. As demonstrated by the case presented herein, inadequate initial evaluation of right-sided pressures delayed the diagnosis and treatment of prosthetic tricuspid valve stenosis.
View details for Web of Science ID A1992JX49800011
View details for PubMedID 1443769
Benzodiazepines, such as lorazepam and midazolam, are frequently administered to surgical intensive care unit (ICU) patients for postoperative sedation. To date, the pharmacology of lorazepam in critically ill patients has not been described. The aim of the current study was to characterize and compare the pharmacokinetics and pharmacodynamics of lorazepam and midazolam administered as continuous intravenous infusions for postoperative sedation of surgical ICU patients.With Institutional Review Board approval, 24 consenting adult surgical patients were given either lorazepam or midazolam in a double-blind fashion (together with either intravenous fentanyl or epidural morphine for analgesia) through target-controlled intravenous infusions titrated to maintain a moderate level of sedation for 12-72 h postoperatively. Moderate sedation was defined as a Ramsay Sedation Scale score of 3 or 4. Sedation scores were measured, together with benzodiazepine plasma concentrations. Population pharmacokinetic and pharmacodynamic parameters were estimated using nonlinear mixed-effects modeling.A two-compartment model best described the pharmacokinetics of both lorazepam and midazolam. The pharmacodynamic model predicted depth of sedation for both midazolam and lorazepam with 76% accuracy. The estimated sedative potency of lorazepam was twice that of midazolam. The predicted C50,ss (plasma benzodiazepine concentrations where P(Sedation > or = ss) = 50%) values for midazolam (sedation score [SS] > or = n, where n = a Ramsay Sedation Score of 2, 3, ... 6) were 68, 101, 208, 304, and 375 ng/ml. The corresponding predicted C50,ss values for lorazepam were 34, 51, 104, 152, and 188 ng/ml, respectively. Age, fentanyl administration, and the resolving effects of surgery and anesthesia were significant covariates of benzodiazepine sedation. The relative amnestic potency of lorazepam to midazolam was 4 (observed). The predicted emergence times from sedation after a 72-h benzodiazepine infusion for light (SS = 3) and deep (SS = 5) sedation in a typical patient were 3.6 and 14.9 h for midazolam infusions and 11.9 and 31.1 h for lorazepam infusions, respectively.The pharmacology of intravenous infusions of lorazepam differs significantly from that of midazolam in critically ill patients. This results in significant delays in emergence from sedation with lorazepam as compared with midazolam when administered for ICU sedation.
View details for Web of Science ID 000170237800003
View details for PubMedID 11506097