Using Methicillin-Resistant Staphylococcus aureus Nasal Screens to Rule Out Methicillin-Resistant S aureus Pneumonia in Surgical Intensive Care Units.

INTRODUCTION: The methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) has a high negative predictive value (NPV). We aimed to understand if there was a difference in the NPV of the MRSA screen in surgical intensive care units (ICUs) and to determine its role in antibiotic de-escalation. METHODS: We performed a single-center, retrospective cohort study of adults with a positive respiratory culture and MRSA nasal PCR admitted to a surgical ICU from 2016 to 2019. Patients were stratified by surgical ICU: cardiothoracic/cardiovascular intensive care unit (CVICU) or transplant/acute care surgery intensive care unit (ACS-ICU). Our primary outcome was the NPV of MRSA screen. Secondary outcome was the duration of empiric MRSA-targeted therapy. RESULTS: We analyzed 61 patients: 42.6% (n = 26) ACS-ICU and 57.4% (n = 35) CVICU. There were no differences in age, comorbidities, prior MRSA infection, recent antibiotic use, immunocompromised status, or renal replacement therapy. At pneumonia diagnosis, more patients in the ACS-ICU were hospitalized ≥5 d (65.4% versus 8.6%, P < 0.0001) and more patients in the CVICU were in septic shock (88.6% versus 34.5%, P < 0.0001) and thrombocytopenic (40% versus 11.5%, P = 0.02). NPV of the PCR was similar (ACS-ICU: 0.92 [0.75-0.98], CV-ICU 0.89 [0.73-0.96]). On multivariable linear regression, the CVICU was associated with longer empiric therapy (ß 1.5, 95% CI 0.8-2.3, P < 0.0001), as was hospitalization for ≥5 d (ß 0.73, 95% CI 0.06-1.39, P = 0.03). CONCLUSIONS: The MRSA nasal PCR screen has a high NPV for ruling out MRSA pneumonia in critically ill surgical patients. However, patients in the CVICU and patients hospitalized ≥5 d had a longer time to de-escalation of MRSA-targeted therapy, potentially due to higher clinical risk profile.

Antimicrobial Stewardship in the ICU.

Increasing rates of infection and multidrug-resistant pathogens, along with a high use of antimicrobial therapy, make the intensive care unit (ICU) an ideal setting for implementing and supporting antimicrobial stewardship efforts. Overuse of antimicrobial agents is common in the ICU, as practitioners are challenged daily with achieving early, appropriate empiric antimicrobial therapy to improve patient outcomes. While early antimicrobial stewardship programs focused on the financial implications of antimicrobial overuse, current goals of stewardship programs align closely with those of critical care providers-to optimize patient outcomes, reduce development of resistance, and minimize adverse outcomes associated with antibiotic overuse and misuse such as acute kidney injury and Clostridioides difficile-associated disease. Significant opportunities exist in the ICU for critical care clinicians to support stewardship practices at the bedside, including thoughtful and restrained initiation of antimicrobial therapy, use of biomarkers in addition to rapid diagnostics, Staphylococcus aureus screening, and traditional microbiologic culture and susceptibilities to guide antibiotic de-escalation, and use of the shortest duration of therapy that is clinically appropriate. Integration of critical care practitioners into the initiatives of antimicrobial stewardship programs is key to their success. This review summarizes key components of antimicrobial stewardship programs and mechanisms for critical care practitioners to share the responsibility for antimicrobial stewardship.

Impact of Serum Phosphate in Mechanically Ventilated Patients With Severe Sepsis and Septic Shock.

BACKGROUND: Hypo- and hyperphosphatemia are common in severe sepsis and septic shock. Published outcome data in patients with phosphate derangements primarily focus on hypophosphatemia and the general critically ill population. This study aimed to determine the impact of serum phosphate on clinical outcomes in patients with severe sepsis and septic shock. METHODS: A retrospective cohort analysis of adult mechanically ventilated patients with severe sepsis or septic shock was performed. Patients were randomly selected from an internal intensive care unit (ICU) database at an academic medical center in the United States and screened for inclusion and exclusion criteria. Time-weighted phosphate was calculated using all phosphate measurements obtained during ICU admission. The associations between time-weighted phosphate and duration of mechanical ventilation, 28-day mortality, and ICU and hospital length of stay were evaluated using linear or logistic regression as appropriate. RESULTS: One-hundred ninety-seven patients were evaluated: 33 were categorized as hypophosphatemia, 123 as normophosphatemia, and 41 as hyperphosphatemia. Patients with time-weighted hyperphosphatemia had a higher Simplified Acute Physiology Score III score and incidence of septic shock. Significantly higher rates of 28-day mortality were observed among those with time-weighted phosphate levels above 3.5 mg/dL. However, both time-weighted hypo- and hyperphosphatemia were associated with decreased duration of mechanical ventilation. For every 0.5 mg/dL increase in time-weighted phosphate referent values from 4.0 to 6.0, the duration of mechanical ventilation decreased by 8% to 26%. For every 0.5 mg/dL decrease in time-weighted phosphate referent values from 3.0 to 1.0, significant decreases in duration of mechanical ventilation ranged from 14% to 41%. CONCLUSION: Time-weighted hyperphosphatemia may be associated with increased mortality in mechanically ventilated patients with severe sepsis or septic shock. However, time-weighted hypo- and hyperphosphatemia were associated with decreased duration of mechanical ventilation. Future studies should further describe the impact of hypo- and hyperphosphatemia on clinical outcomes among critically ill patients with severe sepsis or septic shock.

Individualizing Glycemic Control in the Critically Ill.

Hyperglycemia is a common phenomenon in critically ill patients, even in those without diabetes. Two landmark studies established the benefits of tight glucose control (blood glucose target 80-110 mg/dL) in surgical and medical patients. Since then, literature has consistently demonstrated that both hyperglycemia and hypoglycemia are independently associated with increased morbidity and mortality in a variety of critically ill patients. However, tight glycemic control has subsequently come into question due to risks of hypoglycemia and increased mortality. More recently, strategies targeting euglycemia (blood glucose ≤180 mg/dL) have been associated with improved outcomes, although the risk of hypoglycemia remains. More complex targets (ie, glycemic variability and time within target glucose range) and the impact of individual patient characteristics (ie, diabetic status and prehospital glucose control) have more recently been shown to influence the relationship between glycemic control and outcomes in critically ill patients. Although our understanding has increased, the optimal glycemic target is still unclear and glucose management strategies may require adjustment for individual patient characteristics. As glucose management increases in complexity, we realize that traditional means of using meters and strips and paper insulin titration algorithms are potential limitations to our success. To achieve these complex goals for glycemic control, the use of continuous or near-continuous glucose monitoring combined with computerized insulin titration algorithms may be required. The purpose of this review is to discuss the evidence surrounding the various domains of glycemic control and the emerging data supporting the need for individualized glucose targets in critically ill patients.

Nebulized Heparin for Adult Patients With Smoke Inhalation Injury: A Review of the Literature.

Objective: To review the clinical effects of nebulized heparin and N-acetylcysteine (NAC) in patients with smoke inhalation injury (IHI) and provide recommendations for use. Data Sources: A search of PubMed, MEDLINE, and Scopus databases was completed from database inception through April 15, 2020, using terms: heparin, acetylcysteine, smoke inhalation injury, and burn injury. Study Selection and Data Extraction: All studies pertaining to efficacy and safety of nebulized heparin and/or NAC for IHI in adult patients were evaluated. Reference lists were reviewed for additional publications. Nonhuman studies, non-English, and case report publications were excluded. Data Synthesis: Eight studies were included. Four demonstrated positive outcomes, 3 demonstrated no benefit or possible harm, and 1 assessed safety. Supporting trials treated patients within 48 hours of injury with 10 000 units of nebulized heparin with NAC for 7 days or until extubation. Two trials with negative findings treated patients within 72 hours, or unspecified, with 5000 units of nebulized heparin with NAC for 7 days, while the third used 25 000 units within 36 hours but was grossly underpowered for analysis. Clinical findings include reduced duration of mechanical ventilation and improved lung function with possible increase risk of pneumonia and no evidence of increased bleeding risk. Conclusions: Nebulized heparin may improve oxygenation and reduce duration of mechanical ventilation in IHI. If nebulized heparin is used, 10 000 units every 4 hours alternating with NAC and albuterol at 4-hour intervals is recommended. Sterile technique should be emphasized. Monitoring for bronchospasm or new-onset pneumonia should be considered.

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

INTRODUCTION: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. METHODS: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. RESULTS: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. CONCLUSION: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

Pharmaceutical Cost Savings in the Intensive Care Unit.

Health care costs are rising in the United States with a significant amount of this spend attributed to pharmaceutical costs. The reasons for rising pharmaceutical costs are multifactorial and may include the increase in single source manufacturers of generic medications, drug shortages, the Food and Drug Administration's unapproved drug approval initiative, and generic rebranding. Many of these factors impact the intensive care unit directly creating the need to implement cost-savings strategies to ensure the financial health of an organization and reduce the financial burden for patients. To mitigate rising costs, we have outlined a number of both operational and clinical cost-savings measures derived from the literature and from institutional experience. Engaging the multidisciplinary team in the development and implementation of these initiatives will ensure their success and will maximize their impact.

Remifentanil, ketamine, and fospropofol: a review of alterative continuous infusion agents for sedation in the critically ill.

Sedation and analgesia are integral aspects in the care of critically ill patients admitted to the intensive care unit. In recent years, many of the commonly used sedative agents in the United States have experienced manufacturing and sterility issues leading to decreased availability. In addition, current practice has shifted to providing lighter levels of sedation as clinicians have gained a better understanding of the consequences of prolonged deep sedation. Benzodiazepines have fallen out of favor due to findings including increased delirium and duration of mechanical ventilation. Alterations in end-organ function in critically ill patients may also lead to varied responses to commonly used sedatives. With numerous factors impacting choice of sedation in the intensive care unit, fospropofol, ketamine, and remifentanil have been considered potential alternatives to standard therapy. The purpose of this review was to discuss strategies for the safe and effective use of fospropofol, ketamine, and remifentanil for continuous intravenous sedation in critically ill patients.

The effect of hydrocortisone versus hydrocortisone plus fludrocortisone on duration of shock: A propensity score-weighted analysis.

Background: The 2021 Surviving Sepsis Campaign Guidelines recommend the use of hydrocortisone in patients who remain hemodynamically unstable despite adequate fluid resuscitation and vasopressor therapy. Fludrocortisone has been used concomitantly with hydrocortisone in some studies without a clearly defined role or known clinical benefit. The purpose of this study was to assess the impact of fludrocortisone added to hydrocortisone on shock-free days for septic shock. Methods: A single-center, retrospective propensity score-weighted study was conducted to compare hydrocortisone versus hydrocortisone plus fludrocortisone for septic shock. Adults admitted to the medical intensive care unit (ICU) from 2015 to 2020 were included in the study. All patients received ≥200 mg/day hydrocortisone for at least 24 h ± fludrocortisone initiated within 72 h of vasopressors. The primary outcome was shock-free days by day 14. The secondary outcomes included duration of shock, change in Sequential Organ Failure Assessment (SOFA) score, hospital and ICU length of stay, and all-cause inhospital mortality. Results: A total of 228 patients met inclusion criteria with 212 patients retained after propensity score weighting. There was no difference between groups in 14-day shock-free days (6.3 vs. 6.1 days; P = 0.781). Furthermore, no significant differences were observed for the secondary outcomes of ICU/hospital length of stay, duration of shock, change in SOFA score, and all-cause inhospital mortality. Conclusion: The addition of fludrocortisone to hydrocortisone in septic shock did not increase shock-free days by day 14. These results suggest that the use of hydrocortisone alone may be an adequate adjunctive therapy in septic shock. A prospective randomized controlled trial is needed to confirm results.

Comorbidity-polypharmacy score: a novel adjunct in post-emergency department trauma triage.

OBJECTIVE: Post-emergency department triage of older trauma patients continues to be challenging, as morbidity and mortality for any given level of injury severity tend to increase with age. The comorbidity-polypharmacy score (CPS) combines the number of pre-injury medications with the number of comorbidities to estimate the severity of comorbid conditions. This retrospective study examines the relationship between CPS and triage accuracy for older (≥45y) patients admitted for traumatic injury. METHODS: Patients aged 45y and older presenting to level 1 trauma center from 2005 to 2008 were included. Basic data included patient demographics, injury severity score, morbidity and mortality, and functional outcome measures. CPS was calculated by adding total numbers of comorbid conditions and pre-injury medications. Patients were divided into three triage groups: undertriage (UT), appropriate triage (AT), and overtriage (OT). UT criteria included initial admission to the floor or step-down unit followed by an unplanned transfer to intensive care unit (ICU) within 24h of admission. OT was defined as initial ICU admission for <1d without stated need for ICU level of care (i.e., lack of evidence for tracheal intubation or mechanical ventilation, injury-related hemorrhage, or other traditional ICU indications, such as intracranial bleeding). All other patients were presumed to be correctly triaged. The three triage groups were then analyzed looking for contributors to mistriage. RESULTS: Charts for 711 patients were evaluated (mean age, 63.5y; 55.7% male; mean ISS, 9.02). Of those, 11 (1.55%) met criteria for UT and 14 (1.97%) for OT. The remaining 686 patients had no evidence of mistriage. The three groups were similar in terms of injury severity and GCS. The groups were significantly different with respect to CPS, with UT CPSs (14.9±6.80) being nearly three times higher than OT CPSs (5.14±3.48). There were more similarities between AT and OT groups, with the UT group being characterized by greater number of complications and lower functional outcomes at discharge (all, P<0.05). The UT group had significantly higher mortality (27%) than the AT and OT groups (6% and 0%, respectively). CONCLUSIONS: In the era of medication reconciliation, CPS is easy to obtain and calculate in patients who are not critically injured. This study suggests that CPS may be a promising adjunct in identifying older trauma patients who are more likely to be undertriaged. The significance of our findings is especially important when considering that injury severity in the UT group was similar to that in the other groups. Further evaluation of CPS as a triage tool in acute trauma is warranted.

Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retrospective study.

BACKGROUND: The incidence of multi-drug resistant (MDR) gram-negative (GN) organisms including Pseudomonas and Acinetobacter spp has increased in the last decade, prompting re-evaluation of colistin for the management of these infections. Aerosolized colistin as an adjunct to intravenous therapy is a current option for the management of MDR-GN pneumonia, although data supporting this practice is limited. This study evaluates the efficacy of adjunctive aerosolized colistin in combination with intravenous colistin in critically ill patients with MDR-GN pneumonia. METHODS: A retrospective multi-center cohort analysis comparing critically ill patients with MDR-GN pneumonia who received intravenous colistin (IV) alone or in combination with adjunctive aerosolized colistin (IV/AER) with a primary endpoint of clinical cure at the end of colistin therapy. Secondary endpoints included microbiologic cure, duration of mechanical ventilation, length of stay, and hospital mortality. A post-hoc subgroup analysis was performed for patients with high quality cultures used for diagnosis of MDR-GN pneumonia. Dichotomous data were compared using Fisher's exact test while the student's t-test or Mann-Whitney U test were used for continuous variables. RESULTS: Ninety-five patients met criteria for evaluation with 51 patients receiving IV and 44 receiving IV/AER. Baseline characteristics were similar between the two groups. Twenty patients (39.2%) receiving IV and 24 (54.5%) receiving IV/AER achieved clinical cure (p = 0.135). There was no difference in microbiologic cure rates between the IV and IV/AER colistin groups (40.7vs. 44.4%, p = 0.805). The IV group demonstrated a trend towards higher pneumonia attributable mortality (70.4 vs. 40%, p = 0.055). In the subgroup analysis of patients with high quality respiratory cultures, there was a significantly lower clinical cure rate for those in the IV group as compared to the IV/AER group (31.3 vs. 57.1%, p = 0.033). CONCLUSIONS: Addition of aerosolized colistin to IV colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. Larger, prospective trials are warranted to confirm the benefit of adjunctive aerosolized colistin in critically ill patients with MDR-GN pneumonia.

Performance of different body weights in the Cockcroft-Gault equation in critically ill patients with and without augmented renal clearance: A multicenter cohort.

STUDY OBJECTIVE: The primary objective was to evaluate the performance of the Cockcroft-Gault (CG) equation with different body weights (BWs) compared to a measured creatinine clearance (mCrCl) in an intensive care unit (ICU) population with and without augmented renal clearance (ARC). DESIGN: Multicenter, retrospective cohort. SETTING: Two ICUs in the United States and four ICUs from a previous international observational analysis. PATIENTS: Adult ICU patients admitted from January 1, 2010 to July 30, 2020 with at least one mCrCl collected within the initial 10 days of hospitalization were eligible for inclusion. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the performance of the CG equation in ARC (mCrCl≥130 ml/min/1.73 m2 ) and non-ARC (mCrCl<130 ml/min/1.73 m2 ) patients. Correlation was analyzed by Pearson's correlation coefficient, bias by mean difference, and accuracy by the percentage of patients within 30% of the mCrCl. A total of 383 patients were included, which provided 1708 mCrCl values. The majority were male (n = 239, 62%), median age of 55 years [IQR 40-65] with a surgical diagnosis (n = 239, 77%). ARC was identified in 229 (60%) patients. The ARC group had lower Scr values (0.6 [0.5-0.7] vs. 0.7 [0.6-0.9] mg/dl, p < 0.001) and higher mCrCl (172.8 (SD 39.1) vs. 89.9 mL/min/1.73 m2 (SD 25.4), p < 0.001) compared with the non-ARC group, respectively. Among non-ARC patients there was a moderate correlation (r = 0.33-0.39), moderate accuracy (range 48-58%), and low bias (range of -12.9 to 17.1) among the different BW estimations with the adjusted BW having the better performance. Among ARC patients there was low correlation (r = 0.24-0.28), low to moderate accuracy (range 38-70%), and high bias (range of -58.5 to -21.6). CONCLUSIONS: The CG-adjusted BW had the best performance in the non-ARC patients, while CG performed poorly with any BW in ARC patients. Although the CG equation remains the standard equation for estimating CrCl in the ICU setting, a new, validated equation is needed for patients with ARC.

Characterization of Medication Discrepancies and Interventions Resulting From Pharmacy-Led Medication Reconciliation in the Critical Care Setting.

BACKGROUND: Medication reconciliation has been shown to reduce medication-related errors in hospitalized patients, but the impact of pharmacy-led medication reconciliation in the intensive care unit (ICU) has not been extensively studied. METHODS: This was a retrospective chart review of patients with a pharmacy-led medication reconciliation on admission to an ICU between January 1st and March 31st, 2018. Pharmacy-led medication reconciliations were completed by pharmacists, pharmacy residents, and pharmacy students. The objective of this study was to describe medication discrepancies identified by pharmacy-led medication reconciliation and to evaluate the interventions following. RESULTS: A total of 288 patients were screened and 247 met inclusion criteria. There were 1148 medication discrepancies identified resulting in an average of 4.65 discrepancies per patient. Medication addition (54.25%) and medication deletion (45.75%) were most common. Within 24 hours of medication reconciliation, 214 interventions were made to active orders. No differences were observed between discrepancies identified and type of pharmacy staff completing the medication reconciliation. CONCLUSIONS: This study identified a high rate of medication discrepancies on admission to the ICU. Furthermore, it describes the types of pharmacist interventions following pharmacy-led medication reconciliation. This process may be impactful to incorporate as a standard practice in ICUs and warrants further investigation into value, cost, and pharmacist workflow.

Bleeding risk factors associated with argatroban therapy in the critically ill.

Argatroban is a parenteral direct thrombin inhibitor labeled for anticoagulation in patients with confirmed or suspected heparin-induced thrombocytopenia in the United States. Currently there are no studies evaluating bleeding risk factors in Intensive Care Unit patients.To determine bleeding risk factors associated with argatroban therapy in the critically ill. Critically ill patients admitted between July 2007-June 2008 who received argatroban were included in this retrospective cohort study. The primary endpoint was the incidence of bleeding complications associated with argatroban. Major bleeding was defined as a hemoglobin reduction ≥2 g/dL plus a transfusion of ≥2 units of blood in a 24 h period, or a retroperitoneal, intracranial, prosthetic joint, or other life-threatening bleed. Minor bleeding was any overt bleeding not fitting the major bleeding definition. Secondary outcomes included identifying risk factors for bleeding. Seventy-three patients were included with 16 (21.9%) total bleeding complications, 7 (9.6%) major and 9 (12.3%) minor bleeds. Four risk factors for bleeding were identified by univariate analysis: major surgery prior to or during argatroban therapy (OR = 8.4, 95% CI: 2.3-30.1, p = 0.001), dosing weight >90 kg (OR = 4.8, 95% CI: 1.4-15.8, p = 0.01), total bilirubin >3 mg/dL (OR = 8.1, 95% CI: 2.1-31.1, p = 0.002), and baseline platelets ≤70 K/µL (OR = 4.2, 95 % CI: 1.1-16.3, p = 0.039).Risks and benefits of argatroban should be weighed in patients with major surgery prior to or during argatroban, dosing weight ≥90 kg, total bilirubin ≥3 mg/dL, and baseline platelets ≤70 K/µL.

Early onset delirium incidence and risk factors in hematology oncology patients admitted to the intensive care unit: A retrospective cohort study.

Background: Delirium occurs frequently in intensive care unit (ICU) patients; however, there are limited data evaluating its impact on critically ill hematology-oncology patients. We aimed to determine the incidence and risk factors for early-onset delirium development in hematology-oncology patients admitted to the ICU. Methods: This single-center, retrospective cohort study evaluated the primary outcome of incident delirium within 7 days of ICU admission in adults admitted to the hematology-oncology medical or surgical ICU. Patients with delirium (DEL) were compared to those without (No-DEL) for evaluation of secondary endpoints including hospital mortality, ICU, and hospital length of stay (LOS). Multivariable logistic regression modeling was performed to identify independent risk factors for delirium. Results: Delirium occurred in 125 (51.2%) of 244 patients. Inhospital mortality was significantly higher in the DEL vs. No-DEL group (32.8% vs. 15.1%, P = 0.002). Median (1st and 3rd quartiles) ICU and hospital LOS were significantly longer in the delirium group, respectively (6 [4-10] days vs. 3 [2-5] days, P < 0.001, and 21 [14-36] days vs. 12 [8-22] days, P < 0.001). Higher Sequential Organ Failure Assessment score, high-dose corticosteroids, mechanical ventilation (MV), and brain metastases were each independently, associated with an increased delirium risk. Conclusion: Hematology-oncology patients admitted to the ICU frequently develop delirium. Consistent with literature in nonhematology-oncology critically ill patients, identified independent risk factors for delirium were MV and organ dysfunction. Risk factors unique to the critically ill hematology-oncology patient population include high-dose corticosteroids and brain metastases. Further research is needed to evaluate strategies to mitigate delirium development in this population based on risk assessment.

Perioperative subcutaneous methylnaltrexone does not enhance gastrointestinal recovery after posterior short-segment spinal arthrodesis surgery: a randomized controlled trial.

BACKGROUND CONTEXT: Postoperative ileus is a major barrier to gastrointestinal recovery following surgery. Opioid analgesics likely play an important causative role, particularly in spinal or orthopedic surgeries not involving bowel manipulation. Methylnaltrexone, a peripherally-acting µ-opioid receptor antagonist, is a potential prophylactic treatment. PURPOSE: To assess the influence of perioperative subcutaneous methylnaltrexone administration on gastrointestinal recovery following short-segment lumbar arthrodesis surgeries. DESIGN: This is a randomized, double-blind, controlled trial. PATIENT SAMPLE: Eligible patients undergoing posterior short-segment lumbar arthrodesis surgeries at a single institution between February 2019 and April 2021 were enrolled in this study. OUTCOME MEASURES: The primary outcome measure was time-to-first bowel movement. Secondary outcome measures included time-to-discharge/discharge eligibility. Exploratory outcome measures included daily postoperative opioid consumption and pain scores. METHODS: In this study, eligible patients were enrolled to receive either methylnaltrexone or placebo perioperatively. Time-to-bowel movement, time-to-discharge/discharge eligibility, intra and postoperative analgesic administration, and pain scores were recorded and compared. RESULTS: Eighty two patients in total were enrolled; 41 to the methylnaltrexone and 41 to the placebo group. Both groups were similar in their baseline characteristics. There was no difference in median (range) time-to-bowel movement between the 2 groups [61.8 hours (35.7-93.6) versus 50.7 hours (17.8-110.8), p = .391]. There was also no difference in time-to-discharge/discharge eligibility [105.0 hours (81.0 - 201.3) versus 90.7 (77.5 - 184.5), p=.784]. Finally, there were no differences in either postoperative opioid consumption or numeric rating scores for back, leg, or abdominal pain on postoperative days 0 to 4 (p>.05). CONCLUSIONS: Methylnaltrexone did not accelerate gastrointestinal recovery and did not affect opioid consumption or pain scores following short-segment spinal surgery as compared to placebo. Additional studies will be needed to identify effective opioid receptor antagonist dosing regimens for patients undergoing either short- or long-segment spinal arthrodesis procedures.

Design and feasibility of a double-blind, randomized trial of peri-operative methylnaltrexone for postoperative ileus prevention after adult spinal arthrodesis.

BACKGROUND: Postoperative ileus (POI) is a common complication with no proven prophylactic measures in place. While perioperative opioid use has been implicated in POI development, current treatments fail to target this disease mechanism. Methylnaltrexone (MNTX) has been used to prevent the effects of opioids on the bowel and could reduce the incidence of POI when administered preoperatively. METHODS: In this phase IIb randomized controlled trial, we assessed the effect of perioperative MNTX on time-to-first-bowel movement following spinal arthrodesis surgeries. RESULTS: 82 patients were randomly selected in a 1:1 ratio to be included in either the treatment or placebo groups. Comparison of relevant factors of included patients to patients who refused to participate (n = 21) and to a prior retrospective series (n = 241) revealed no differences in age, male sex, liver disease, and number of surgical levels. Overall treatment fidelity (98% adherence) and retention (100% at one-month follow-up) were high. The predicted POI incidence (9.3-11.1%) was also equivalent to a prior retrospective series. However, the overall observed POI incidence (3.7%) was lower than expected, which could reflect a superimposed 'trial effect' related to standardized care in a research setting. CONCLUSIONS: Since exposure to significant opioid doses represents a barrier to enhanced recovery after surgery, the results of this innovative trial may provide further guidance for the peri-operative use of opioid-receptor blockers. Here, we show that MNTX can be effectively administered in the peri-operative period with appropriate follow-up achieved in a representative population of patients undergoing spinal surgery. TRIAL REGISTRATION NUMBERS: Clinicaltrials.gov - NCT03852524 and Institutional Review Board - 2018H0260.

High-dose dexmedetomidine for sedation in the intensive care unit: an evaluation of clinical efficacy and safety.

BACKGROUND: Dexmedetomidine is an α(2)-receptor agonist used for sedation in the intensive care unit (ICU). Although dexmedetomidine is labeled for sedation in critically ill patients at doses up to 0.7 µg/kg/h, recent studies have used more liberal dosing regimens. However, to our knowledge, no study has assessed the clinical impact of doses greater than 0.7 µg/kg/h when compared to doses within the Food and Drug Administration--approved labeling. OBJECTIVE: To compare the clinical efficacy and safety of high (HD) and low (LD) doses of dexmedetomidine for sedation in the ICU. METHODS: This retrospective study included a sample of patients who received dexmedetomidine in medical, surgical, medical/surgical, and cardiothoracic ICUs between January 1, 2008, and December 1, 2009. Patients were included in the LD group if their maximum dose was less than 0.7 µg/kg/h or in the HD group if any dose was more than 0.7 µg/kg/h. Efficacy was determined by the percentage of Richmond Agitation and Sedation Scale (RASS) scores for each patient maintained at goal sedation (-1 to +1), and safety was determined by the incidence of hypotension and bradycardia. RESULTS: Forty-three of 133 patients received HD dexmedetomidine. Patients in the LD group had a significantly higher percentage of RASS scores at goal (60.0% vs 48.6%; p = 0.03), while those in the HD group experienced a higher percentage of RASS scores classified as undersedated (19.2% vs 4.9%; p = 0.001). There was no significant difference in the incidence of hypotension or bradycardia between groups. CONCLUSIONS: Patients treated with HD dexmedetomidine had fewer RASS scores at goal. Our data suggest that increasing the dose of dexmedetomidine may not enhance sedation efficacy or lead to an increased incidence of adverse effects. Patients who have not achieved goal sedation at doses of 0.7 µg/kg/h or less may not respond further to increased doses.

Clinical outcomes following burn injury across the continuum of chronic glycemic control.

Diabetes has been associated with poor outcomes following burn injury. There is limited data related to prediabetes in burn injury, and no studies to date have compared clinical outcomes inpatients without diabetes, with prediabetes, and with diabetes. Therefore, this study aimed to compare clinical outcomes after burn injury across the continuum of pre-injury glucose control. A propensity score weighted cohort study of adult patients admitted for initial management of burn injury was performed. Patients were categorized as no diabetes, prediabetes or diabetes based on their admission hemoglobin A1c and past medical history. The primary outcome was length of stay per percent Total Body Surface Area (TBSA) burn. Secondary outcome measures included length of stay, all-cause hospital mortality, disposition at discharge, re-grafting of same site, and amputations. A total of 2450 patients were screened; 1137 patients were included for evaluation (236 diabetes, 191 prediabetes, 710 no diabetes). After inverse probability weighing to adjust for potentially confounding factors, patients in the diabetes group had longer length of stay/%TBSA burn than both the no diabetes group (ratio of geometric means (95% CI) = 1.65 (1.25, 2.18), p < 0.001) and the prediabetes group (ratio (95% CI) = 1.49 (1.10, 2.02), p = 0.01). No statistically significant differences in secondary outcomes were observed between groups other than a higher rate of amputations in the diabetes group (2.7%) compared to the no diabetes (0.7%, p = 0.047) and prediabetes (0%, p = 0.04) groups. Further studies are needed to delineate the differences across the continuum of pre-injury glucose control in order to identify mechanisms to optimize burn-related outcomes.