Brian L. Erstad

Medication errors and adverse drug events in an intensive care unit : Direct observation approach for detection

Objective:To determine the incidence and preventability of medication errors and potential/actual adverse drug events. To evaluate system failures leading to error occurrence. Design:Prospective, direct observation study. Setting:Tertiary care academic medical center. Patients:Patients in a medical/surgical intensive care unit. Interventions:Observers would intervene only in the event that the medication error would cause substantial patient harm or discomfort. Measurements and Main Results:The observers identified 185 incidents during a pilot period and four phases totaling 16.5 days (33 12-hr shifts). Two independent evaluators concluded that 13 of 35 (37%) actual adverse drug events were nonpreventable (i.e., not medication errors). An additional 40 of the remaining 172 medication errors were judged not to be clinically important. Of the 132 medication errors classified as clinically important, 110 (83%) led to potential adverse drug events and 22 (17%) led to actual, preventable adverse drug events. There was one error (i.e., resulting in a potential or actual, preventable adverse drug event) for every five doses of medication administered. The potential adverse drug events mostly occurred in the administration and dispensing stages of the medication use process (34% in each); all of the actual, preventable adverse drug events occurred in the prescribing (77%) and administration (23%) stages. Errors of omission accounted for the majority of potential and actual, preventable adverse drug events (23%), followed by errors due to wrong dose (20%), wrong drug (16%), wrong administration technique (15%), and drug-drug interaction (10%). Conclusions:Using a direct observation approach, we found a higher incidence of potential and actual, preventable adverse drug events and an increased ratio of potential to actual, preventable adverse drug events compared with studies that used chart reviews and solicited incident reporting. All of the potential adverse drug events and approximately two thirds of the actual adverse drug events were judged to be preventable. There was one preventable error for every five doses of medication administered; most errors were due to dose omission, wrong dose, wrong drug, wrong technique, or interactions.

Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient

Objective:To update the 2002 version of “Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient.” Design:A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. Methods:Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. Results:The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

A Paradigm for Consensus: The University Hospital Consortium Guidelines for the Use of Albumin, Nonprotein Colloid, and Crystalloid Solutions

OBJECTIVE To develop contemporary, comprehensive guidelines for the appropriate and efficient use of albumin, nonprotein colloid, and crystalloid solutions. DESIGN A systematic, literature-based, consensus exercise employing a modified Delphi method. PARTICIPANTS Thirty-one medical and allied health professionals from 26 University Hospital Consortium (Oak Brook, Ill) member institutions were initially chosen to participate. Participants were selected on the basis of their recognized research in the use of albumin, nonprotein colloid, and crystalloid solutions, and/or experience in the review of appropriateness of such use. A total of 24 participants completed the exercise. MAIN OUTCOME MEASURES Group responses were statistically analyzed in an iterative consensus development process. Five separate questionnaire rounds were designed to establish criteria for the appropriate use of albumin, nonprotein colloid, and crystalloid solutions. RESULTS Consensus guidelines were developed outlining the appropriate use of these products for 12 clinical indications, including hemorrhagic shock, nonhemorrhagic (maldistributive) shock, hepatic resection, thermal injury, cerebral ischemia, nutritional intervention, cardiac surgery, hyperbilirubinemia of the newborn, cirrhosis and paracentesis, nephrotic syndrome, organ transplantation, and plasmapheresis. CONCLUSIONS The Delphi method, a systematic, literature-based consensus process, was shown to be useful in the development of complex clinical practice guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions. It is anticipated that the guidelines will assist health care providers to develop local institutional policies and procedures for the appropriate and efficient use of albumin and albumin alternatives. Institutions reviewing and updating existing local guidelines may use the University Hospital Consortium guidelines as a model for comparison.

Dosing of medications in morbidly obese patients in the intensive care unit setting

ObjectiveTo derive recommendations for the dosing of commonly used medications in the morbidly obese patient in the ICU.Data sourcesArticles were obtained through computerized searches involving MEDLINE. The bibliographies of retrieved publications and textbooks were reviewed for additional references.Study selectionAll studies involving the pharmacokinetics or pharmacodynamics of medications in obese subjects or patients.Data extractionThe emphasis was on studies involving morbidly obese patients but, in the absence of such data, investigations involving lesser forms of obesity were extracted.Data synthesisThere is a paucity of data upon which to make recommendations for dosing commonly used medications in the morbidly obese patient in the ICU, although recommendations were provided based on the available information.ConclusionsThere is clearly a need for more investigations involving dosing regimens of medications in the morbidly obese population. Until such studies are available, the clinician must try to derive the best dosing regimens for medications based on the limited pharmacokinetic data available for some agents and clinical judgement.

Opioid Conversions in Acute Care

Objective: To discuss the historical basis and limitations of opioid conversion tables, review the relevant literature, and establish an evidence-based equianalgesic dose ratio (EDR) table for performing conversions in the acute care setting. Data Sources: Articles were identified through searches of MEDLINE (1966–January 2007) using the key words opioid, tolerance, conversion, dose, equianalgesic, equipotent, acute care, morphine, hydromorphone, fentanyl, methadone, and oxycodone. Additional references were located through a review of the bibliographies of articles cited and references cited in conversion tables. Study Selection and Data Extraction: All data sources identified were evaluated, and all information deemed relevant was included, with the exception of case series and case reports when higher level evidence was available. Data Synthesis: Opioid conversion tables are published in major textbooks, medical references, national guidelines, and review articles. Some conversion tables do not accurately reflect the dose ratios for which evidence is available. There is marginal evidence-based clinical data to support the dose ratios cited in these tables, particularly in the acute care setting where the clinical status of patients often changes rapidly. The barriers when performing route and opioid-to-opioid conversions in the acute care setting are formidable, but EDRs are provided, based on the best available evidence. Conclusions: In the acute care setting, calculation of dose ratios for opioids, based solely on opioid conversion tables, is an oversimplification of pain management, with a potential for adverse consequences. The calculation of EDRs is one step in an interdisciplinary process that must take into account patient- and institution-specific factors.

Medication errors involving continuously infused medications in a surgical intensive care unit.

ObjectiveTo document the incidence of medication errors related to medications administered by continuous infusion. DesignObservational study. SettingSixteen-bed surgical intensive care unit. Measurements and Main ResultsAll continuous infusions in the surgical intensive care unit were evaluated at least once daily for correct flow-sheet charting, concentration, infusion rate, and dose administered, as well as patients’ heights and weights (actual, ideal, and “dry”). Collected information was examined to determine the error rate, types of errors occurring, and weight used for dose calculation. Variations inpatient weight measures were compared. Seventy-one patients with 202 total infusions were observed. Errors involving continuously infused medications in our surgical intensive care unit occurred at a rate of 105.9 per 1,000 patient days. For nonweight-based infusions, 94% of doses were delivered correctly. Slightly >10% of the doses administered for weight-based infusions (dose based on dry body weight) were incorrect. Significant differences were found between the weight measurements recorded, but this did not translate into statistically significant differences in the apparent calculated doses delivered. ConclusionsMedications delivered by continuous infusion, particularly those that are weight based, can contribute to medication errors in the intensive care unit. A large proportion (87.6%) of doses for weight-based infusions was calculated based on estimated or unreliable admission weights. There were no severe consequences resulting from the errors observed in this 1 month investigation; however, depending on the pharmacokinetic characteristics of the drug being administered, there is a potential to deliver artificially low or high doses resulting in subtherapeutic or adverse effects.

Pain Management Principles in the Critically Ill

This article addresses conventional pharmacologic and nonpharmacologic treatment of pain in patients in ICUs. For the critically ill patient, opioids have been the mainstay of pain control. The optimal choice of opioid and dosing regimen for a specific patient varies depending on factors such as the pharmacokinetics and physicochemical characteristics of an opioid and the bodys handling of the opioid, concomitant sedative regimen, potential or actual adverse drug events, and development of tolerance. The clinician must appreciate that favorable pharmacokinetic properties such as a short-elimination half-life do not necessarily translate into clinical advantages in the ICU setting. A variety of medications have been proposed as alternatives or adjuncts to the opioids for pain control that have unique considerations when contemplated for use in the critically ill patient. Most have been relatively unstudied in the ICU setting, and many have limitations with respect to availability of the GI route of administration in patients with questionable GI absorptive function. Nonpharmacologic, complementary therapies are low cost, easy to provide, and safe, and many clinicians can implement them with little difficulty or resources. However, the evidence base for their effectiveness is limited. At present, insufficient research evidence is available to support a broad implementation of nonpharmacologic therapies in ICUs.

Direct observation approach for detecting medication errors and adverse drug events in a pediatric intensive care unit.

Objective: To determine the incidence, type, and stage of occurrence of medication errors and potential and actual adverse drug events (ADEs) in a pediatric intensive care unit (ICU) using trained observers. The preventability and severity of ADEs and the system failures leading to medication error occurrence were also investigated. Design: Prospective, direct observation study. Setting: A 16-bed pediatric medical/surgical ICU at a tertiary care academic medical center. Patients: One enrolled nurse caring for at least one pediatric ICU patient age <18 yrs was randomly chosen during each observation period. Interventions: Observers would intervene only in the event that the medication error would cause substantial patient harm or discomfort. Measurements and Main Results: Medication errors and potential and actual ADEs were identified throughout the entire medication use process. The 26 12-hr observation periods included 357 reviewed written orders and 263 observed doses. The study observers identified 58 incidents, which were subsequently classified by the evaluators according to clinical importance, severity, and preventability. Fifty-two of these incidents were considered medication errors; six incidents were determined to be nonpreventable ADEs. Of the 52 medication errors, 42 (81%) were considered clinically important. Potential ADEs comprised 35 (83%) of these important medication errors; the other seven (17%) were classified as actual, preventable ADEs. Overall, the actual and potential ADE rate occurred at 3.6 events and 9.8 events per 100 orders, respectively. Conclusions: Our medication error rate was similar to that of previous pediatric ICU studies that used the direct observation method for reporting but higher than the rates in previous studies using other detection techniques such as voluntary incident reporting. Periodic direct observation and other ongoing data collection methods such as voluntary incident reporting have the potential to be complementary approaches to medication error and ADE detection.

A Prospective Observational Study of Medication Errors in a Tertiary Care Emergency Department

STUDY OBJECTIVE We determine the rate and severity of medication errors, as well as factors associated with error occurrence in the emergency department (ED). METHODS This was a prospective observational study conducted between May 1, 2008, and February 1, 2009. The pharmacist observer was present in the ED for 28 shifts (12 hours each). Information was collected on the medication use process by observing the activities of nurses caring for the patients. Errors were categorized by severity. Logistic regression was used to analyze factors associated with a risk of medication error. RESULTS The observer identified 178 medication errors in 192 patients during the data collection period. At least 1 error occurred in 59.4% of patients, and 37% of patients overall had an error that reached them. No errors in the study resulted in permanent harm to the patient or contributed to initial or prolonged hospitalization; however, interventions were performed to prevent patient harm that likely influenced the severity of error. Errors categorized according to stage were prescribing (53.9%), transcribing (10.7%), dispensing (0.6%), and administering (34.8%). Variables predictive of medication errors were boarded patient status (odds ratio [OR] 2.15; 95% confidence interval [CI] 1.03 to 4.5), number of medication orders (OR 1.25; 95% CI 1.12 to 1.39), number of medications administered (OR 1.22; 95% CI 1.07 to 1.38), and nursing employment status (less error if full time) (OR 0.37; 95% CI 0.16 to 0.86). CONCLUSION Medication errors in the ED are common, and most errors occur in the prescribing and administering phases. Boarded patient status, increasing number of medications orders, increasing number of medications administered, and part-time nursing status are associated with an increased risk of medication error.

Time to positive culture and identification for Candida blood stream infections

Candidemia and delay to appropriate therapy contribute to increased morbidity and mortality. Current literature addresses the delay between blood culture collection and final identification; however, it fails to delineate differences among species. The purpose of this study was to quantify the time to yeast detection and identification relative to blood culture collection and determine whether differences exist among species. In this retrospective study, all cases of Candida isolation for 2 years were reviewed. The time delays between blood culture and detection of Candida growth were quantified as well as the additional time required for final species identification. Initiation of antifungal therapy was assessed in relation to culture collection, detection of yeast, and final identification. The appropriateness of therapy at each time point was also analyzed. Most Candida infections were caused by either Candida albicans (n = 43) or Candida glabrata (n = 27). Mean time to positive yeast detection for C. albicans was 35.3 +/- 18.1 h, whereas that of C. glabrata was 80.0 +/- 22.4 h (P < 0.0001). Mean time to final identification for C. albicans was 85.8 +/- 30.9, whereas that of C. glabrata was 154 +/- 43.8 h (P < 0.0001). Mean time to appropriate therapy for C. albicans isolates was 43.3 +/- 27.6 h compared with 98.1 +/- 38.3 h (P < 0.0001) for C. glabrata isolates. The time delay between blood culture collection and yeast detection as well as final identification was significantly longer for C. glabrata isolates when compared with C. albicans. As a result, mean time to appropriate antifungal therapy was significantly longer in patients with C. glabrata isolates.