Evaluating the incidence of acute kidney injury and gentamicin synergy dosing for endocarditis.

Objectives: Current infective endocarditis guidelines recommend two different gentamicin synergy dosing strategies for selected Gram-positive organisms. The purpose of this analysis was to evaluate the incidence of acute kidney injury (AKI) with gentamicin synergy dosing, comparing divided-daily and once-daily dosing strategies for infective endocarditis (IE). Methods: Groups were split into patients who received gentamicin divided-daily dosing and once-daily (3 mg/kg) dosing for Gram-positive IE. The primary outcome was the incidence of AKI defined by RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria after starting gentamicin. A multivariable logistic regression analysis was performed to identify possible independent predictors of developing AKI. Notable secondary outcomes included hospital length of stay, need for gentamicin dose adjustments based on therapeutic drug monitoring, and assessment of each case of AKI using the Naranjo algorithm. Results: The incidence of AKI was significantly higher in the divided-daily group compared with the once-daily group (52.5% versus 13%, P < 0.01). The divided-dosing group had significantly longer median [IQR] hospital length of stay (19 days [12:29] versus 13.5 days [9:22], P < 0.01) and a greater number of patients who required dose adjustments (76.2% versus 21.7%, P < 0.01). The multivariable regression analysis showed that the divided-dosing strategy, duration and institution were independently associated with incidence of AKI. Conclusions: This analysis suggests a lower incidence of AKI in the treatment of endocarditis with gentamicin synergy dosed once-daily compared with a divided-daily dosing. Further studies are warranted to assess if there is a difference in efficacy between gentamicin synergy dosing strategies and in gentamicin compared with no gentamicin regimens for IE.

Prevalence, risk factors, and outcomes associated with delayed second doses of antibiotics in sepsis at a large academic medical center.

Objective: To evaluate the prevalence, risk factors, and clinical impact of delays in second doses of antibiotics in patients with sepsis. Design: Single-center, retrospective, observational study. Setting: Large teaching hospital. Patients: Adult patients who triggered an electronic sepsis alert in the emergency department (ED), received ≥2 doses of vancomycin or an antipseudomonal beta-lactam, and were discharged with an ICD-10 sepsis code. Methods: We assessed the prevalence of delays in second doses of antibiotics by ≥25% of the recommended dose interval and conducted multivariate regression analyses to assess for risk factors for delays and in-hospital mortality. Results: The cohort included 449 patients, of whom 123 (27.4%) had delays in second doses. In-hospital death occurred in 31 patients (25.2%) in the delayed group and 71 (21.8%) in the non-delayed group (p = 0.44). On multivariate analysis, only location in a non-ED unit at the time second doses were due was associated with delays (OR 2.75, 95% CI 1.20-6.32). In the mortality model, significant risk factors included malignant tumor, respiratory infection, and elevated Sequential Organ Failure Assessment (SOFA) score but not delayed second antibiotic doses (OR 1.19, 95% CI 0.69-2.05). In a subgroup analysis, delayed second doses were associated with higher mortality in patients admitted to non-intensive care units (ICUs) (OR 4.10, 95% CI 1.32-12.79). Conclusions: Over a quarter of patients with sepsis experienced delays in second doses of antibiotics. Delays in second antibiotic doses were not associated with higher mortality overall, but an association was observed among patients admitted to non-ICUs.

Evaluation of Dexmedetomidine as an Adjunct to Phenobarbital for Alcohol Withdrawal in Critically Ill Patients.

INTRODUCTION: Dexmedetomidine (DEX) is commonly used with benzodiazepines for the management of alcohol withdrawal syndrome (AWS), but limited data exist regarding its use with phenobarbital (PHB). This analysis evaluated the utility of DEX in addition to PHB for AWS in adult patients admitted to the intensive care unit (ICU). METHODS: This was a single-center, retrospective cohort analysis of critically ill adult patients who received PHB plus either DEX or different adjunctive therapies (NO-DEX) for AWS between 2018 and 2021. Patients were excluded if they had underlying altered mental status or seizure disorder unrelated to AWS or received PHB at outside hospitals. Coarsened exact matching (CEM) was performed to match patients on baseline characteristics in a 1:1 ratio. The primary outcome was ICU length of stay (LOS). A multivariate linear regression analysis was performed to assess the effects of DEX on ICU LOS when accounting for confounders. Secondary outcomes included days with delirium and incidence of mechanical ventilation after PHB administration. RESULTS: Of the 606 encounters evaluated, 197 met criteria for inclusion. After CEM, 56 encounters remained in each group for analysis. The median ICU LOS was 97.2 [50.1:139.5] hours for the DEX group and 47.5 [28.8:88.1] hours for the NO-DEX group (P = .002). The multivariate linear regression analysis showed the use of DEX (P = .008) was independently associated with an increased ICU LOS by 49.8 h. The DEX group had higher rates of total delirium days (208 vs 143 days, P < .001) and a higher incidence of mechanical ventilation after PHB administration (32% vs 9%, P < .001). CONCLUSION: This analysis suggests the use of adjunctive DEX with PHB for AWS was associated with a prolonged ICU LOS. Additional studies are needed to further understand the role of adjunctive DEX in the treatment of AWS in critically ill patients.

Evaluating the Safety of Continuous Infusion Lidocaine for Postoperative Pain.

OBJECTIVES: The aim was to evaluate the safety of intravenous lidocaine for postoperative pain and the impact on opioid requirements and pain scores. MATERIALS AND METHODS: This was a single-center, retrospective, single-arm analysis of adult patients who received intravenous lidocaine for postoperative pain from January 2016 to December 2019. Patients were excluded if they received lidocaine for any indication other than pain or if lidocaine was only given intraoperatively. The primary outcome of this analysis was to determine the incidence of adverse effects (AEs) and the reason for discontinuation of lidocaine. Secondary outcomes included median daily pain scores (visual analog scale and Critical-Care Pain Observation Tool) and opioid consumption (daily morphine milligram equivalents) 24 hours before infusion and during day 1. RESULTS: A total of 452 patients were evaluated of which 298 (65.9%) patients met inclusion criteria. Of the 154 patients excluded, 153 did not receive lidocaine postoperatively. The median duration of infusion was 34 [20:48] hours with a median initial and maintenance rate of 1 mg/kg/h dosed on ideal body weight. In our analysis, 174 (58.4%) patients had a documented AE during infusion and 38 (12.8%) had lidocaine discontinued because of an AE. The most common AE was nausea in 62 (20.8%) patients and the most common reason for discontinuation was confusion in 8 (2.7%) patients. Daily morphine milligram equivalents (P<0.001) and visual analog scale (P<0.001) significantly decreased when comparing 24 hours before infusion and day 1. CONCLUSION: Although a majority of patients receiving lidocaine for postoperative pain experienced an AE, this did not result in discontinuation in most patients.

Performance and outcomes of transvenous rotational lead extraction: Results from a prospective, monitored, international clinical study.

BACKGROUND: Transvenous lead extraction (TLE) plays a critical role in managing patients with cardiovascular implantable electronic devices. Mechanical TLE tools, including rotational sheaths, are used to overcome fibrosis and calcification surrounding leads. Prospective clinical data are limited regarding the safety and effectiveness of use of mechanical TLE devices, especially rotational tools. OBJECTIVE: To prospectively investigate the safety and effectiveness of mechanical TLE in real-world usage. METHODS: Patients were enrolled at 10 sites in the United States and Europe to evaluate the use of mechanical TLE devices. Clinical success, complete procedural success, and complications were evaluated through follow-up (median, 29 days). Patient data were source verified and complications were adjudicated by an independent clinical events committee (CEC). RESULTS: Between October 2018 and January 2020, mechanical TLE tools, including rotational sheaths, were used to extract 460 leads with a median indwell time of 7.4 years from 230 patients (mean age 64.3 ± 14.4 years). Noninfectious indications for TLE were more common than infectious indications (61.5% vs 38.5%, respectively). The extracted leads included 305 pacemaker leads (66.3%) and 155 implantable cardioverter-defibrillator leads (33.7%), including 85 leads with passive fixation (18.5%). A bidirectional rotational sheath was needed for 368 leads (88.0%). Clinical success was obtained in 98.7% of procedures; complete procedural success was achieved for 96.3% of leads. CEC-adjudicated device-related major complications occurred in 6 of 230 (2.6%) procedures. No isolated superior vena cava injury or procedural death occurred. CONCLUSION: This prospective clinical study demonstrates that use of mechanical TLE tools, especially bidirectional rotational sheaths, are effective and safe.

Safety of Intravenous Push Lacosamide Compared With Intravenous Piggyback at a Tertiary Academic Medical Center.

BACKGROUND: There are limited data regarding the incidence of adverse events associated with administering lacosamide by intravenous push (IVP) compared with IV piggyback (IVPB). OBJECTIVE: The objective of this analysis was to compare the safety profile, including cardiovascular effects, sedative effects, and IV site reactions of IVP and IVPB lacosamide administration. METHODS: A retrospective pre/post cohort analysis comparing patients who received lacosamide via IVP and IVPB was conducted. Safety end points included hypotension, bradycardia, medication-related sedation, and IV site reactions. The relationship between patient characteristics and the incidence of safety end points was analyzed using the Student t-test and χ2 test as appropriate. RESULTS: Bradycardia occurred after 0.19% of IVP administrations and 1.09% of IVPB administrations assessed (P = 0.07). Hypotension was observed in 3.16% of IVP administrations compared to 1.59% in the IVPB cohort (P = 0.12). Post lacosamide-related sedation was noted in 11.32% and 11.68% of the IVP and IVPB cohorts, respectively (P = 0.87). Infusion site reaction rates of 1.80% and 0.84% were documented in the IVP and IVPB cohorts, respectively (P = 0.33). Of note, only 1 adverse event required clinical intervention. One 200-mg dose in the IVP cohort required a fluid bolus postadministration. CONCLUSION AND RELEVANCE: IVP lacosamide was associated with a similar incidence of cardiovascular, neurological, and infusion site-related adverse events compared with IVPB, in which nearly every adverse event was deemed clinically insignificant. Lacosamide administered via IVP may be considered a safe alternative method of administration in the acute care setting.

Evaluation of the Efficacy and Safety of Inhaled Epoprostenol and Inhaled Nitric Oxide for Refractory Hypoxemia in Patients With Coronavirus Disease 2019.

OBJECTIVES: The objectives of this study were to evaluate the efficacy and safety of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019. DESIGN: Retrospective single-center study. SETTING: ICUs at a large academic medical center in the United States. PATIENTS: Thirty-eight adult critically ill patients with coronavirus disease 2019 and refractory hypoxemia treated with either inhaled epoprostenol or inhaled nitric oxide for at least 1 hour between March 1, 2020, and June 30, 2020. INTERVENTIONS: Electronic chart review. MEASUREMENTS AND MAIN RESULTS: Of 93 patients screened, 38 were included in the analysis, with mild (4, 10.5%), moderate (24, 63.2%), or severe (10, 26.3%), with acute respiratory distress syndrome. All patients were initiated on inhaled epoprostenol as the initial pulmonary vasodilator and the median time from intubation to initiation was 137 hours (68-228 h). The median change in Pao2/Fio2 was 0 (-12.8 to 31.6) immediately following administration of inhaled epoprostenol. Sixteen patients were classified as responders (increase Pao2/Fio2 > 10%) to inhaled epoprostenol, with a median increase in Pao2/Fio2 of 34.1 (24.3-53.9). The mean change in Pao2 and Spo2 was -0.55 ± 41.8 and -0.6 ± 4.7, respectively. Eleven patients transitioned to inhaled nitric oxide with a median change of 11 (3.6-24.8) in Pao2/Fio2. A logistic regression analysis did not identify any differences in outcomes or characteristics between the responders and the nonresponders. Minimal adverse events were seen in patients who received either inhaled epoprostenol or inhaled nitric oxide. CONCLUSIONS: We found that the initiation of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019, on average, did not produce significant increases in oxygenation metrics. However, a group of patients had significant improvement with inhaled epoprostenol and inhaled nitric oxide. Administration of inhaled epoprostenol or inhaled nitric oxide may be considered in patients with severe respiratory failure secondary to coronavirus disease 2019.

Evaluation of Sedation Outcomes Following Increased Dexmedetomidine Use in the ICU.

To evaluate sedation practices following a dexmedetomidine guideline update in the ICU. DESIGN: Single-center, retrospective chart review. SETTING: Tertiary academic medical center. PATIENTS: Patients were included in this analysis if they were admitted to the ICU and were ordered for continuous infusion sedatives or opioids from September to November 2016 (PRE) and from September to November 2017 (POST). Patients were excluded from this analysis if they met any of the following criteria: mechanical ventilation less than 12 hours, admitted with acute neurologic injury, burn of greater than 20% total body surface area, chronic tracheostomy, admitted to the neuroscience or cardiac surgery ICU, on extracorporeal membrane oxygenation support, or received an infusion of neuromuscular blockers. INTERVENTIONS: Patients admitted during a restricted dexmedetomidine prescribing guideline were compared with patients admitted during an expanded prescribing guideline. MEASUREMENTS AND MAIN RESULTS: Of the 1,426 patients evaluated for inclusion, 427 patients met the criteria in this analysis. Of these, 217 patients were in the PRE and 210 patients in the POST. A majority of patients were excluded for admission to neuroscience or cardiac surgery ICU. Dexmedetomidine was used in 13.8% of encounters in the PRE and 51.9% of encounters in the POST (p < 0.001). The median duration of mechanical ventilation was 49 hours (24-110 hr) in the PRE and 47.5 hours (26-98 hr) in the POST (p = 0.8). ICU length of stay was a median of 136 and 121 hours in the PRE and POST, respectively (p = 0.2). The median hospital length of stay was 296 and 326 hours in the PRE and POST, respectively (p = 0.35). After controlling for possible confounders, ventilation time remained unchanged between the PRE and POST (p = 0.98). CONCLUSIONS: The expansion of a hospital dexmedetomidine prescribing guideline resulted in an increased use of dexmedetomidine but was not associated with a difference in length of mechanical ventilation.

Prevalence of fracture and fragment embolization of Bard retrievable vena cava filters and clinical implications including cardiac perforation and tamponade.

BACKGROUND: Vena cava filters represent an alternative treatment option for patients with contraindications to anticoagulation, or they might serve as adjunctive treatment for continued emboli despite anticoagulation. The fracture of a filter strut with subsequent end-organ embolization is a rarely reported but potentially life-threatening occurrence. METHODS: We sought to determine the prevalence of fracture and embolization of the Bard Recovery (first generation) and the Bard G2 (second generation) vena cava filters. A retrospective, single-center, cross-sectional study was conducted by evaluating all patients who received either a Bard Recovery or Bard G2 filter from April 2004 until January 2009. A total of 189 patients had undergone implantation: 1 pregnant woman and 35 patients who died were excluded from our study. In addition, 10 patients who had the filter removed were also excluded. Ultimately, 80 patients participated in the trial. Subjects underwent fluoroscopy to assess the filter's integrity. Embolized struts were localized by fluoroscopy. Echocardiography and cardiac computed tomography were performed in patients with fragment embolization to the heart. RESULTS: Thirteen of 80 patients had at least 1 strut fracture (16%). At least 1 strut in 7 of the 28 Bard Recovery filters fractured and embolized (25%). In 5 of these 7 cases, patients had at least 1 fragment embolize to the heart (71%). Three patients experienced life-threatening symptoms of ventricular tachycardia and/or tamponade, including 1 patient who experienced sudden death at home. Six of 52 Bard G2 filters fractured (12%). In 2 of these 6 cases, the patients had asymptomatic end-organ fragment embolization. CONCLUSION: The Bard Recovery and Bard G2 filters had high prevalences of fracture and embolization, with potentially life-threatening sequelae.

Speckle-tracking strain echocardiography for detecting cardiac dyssynchrony in a canine model of dyssynchrony and heart failure.

Multiple echocardiographic criteria have been proposed to diagnose mechanical dyssynchrony in patients with heart failure without being validated against a model of cardiac dyssynchrony with heart failure. This study examines which of these methods can detect dyssynchrony in a canine model. Adult mongrel dogs underwent His-bundle ablation and right-ventricular pacing for 4 wk at either 110 bpm to induce dyssynchrony without heart failure (D group, n = 12) or 170 bpm to induce dyssynchrony with heart failure (DHF group, n = 9). To induce heart failure with narrow QRS, atria were paced at 190 bpm for 4 wk (HF group, n = 8). Tissue Doppler imaging (TDI) and two-dimensional echocardiography were performed at baseline and at end of study. Standard deviation of time to peak systolic velocity (color-coded TDI), time to peak S wave on pulse-wave TDI, time to peak radial and circumferential strain by speckle-tracking analysis (E(rr) and E(cc), respectively), and septal-to-posterior wall motion delay on M mode were obtained. In D group, only E(rr) and E(cc) were increased by dyssynchrony. In contrast, all the echocardiographic parameters of dyssynchrony appeared significantly augmented in the DHF group. Receiver-operator curve analysis showed good sensitivity of E(rr) (90%) and E(cc) (100%) to detected dyssynchrony without heart failure and excellent sensitivity and specificity of E(rr) and E(cc) to detect dyssynchrony with heart failure. Radial strain by speckle tracking is more accurate than TDI velocity to detect cardiac dyssynchrony in a canine model of dyssynchrony with or without heart failure.

Cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) addresses abnormal left ventricular (LV) activation that produces detrimental effects on cardiac systolic and diastolic function. CRT improves symptoms and ventricular performance, promotes reverse remodeling, and decreases mortality and hospitalization in patients with congestive heart failure (CHF). Atrial-synchronized biventricular stimulation reverses many of the temporal delays in mechanical activation associated with LV dysfunction and conduction system disease. The therapy evolved from anecdotal application through surgical implantation of LV pacing leads to transvenous delivery of LV pacing leads for use with dedicated CRT devices. The controlled clinical trials included specific patient groups, and provided data leading to widely adopted indications for the therapy. Current indications exclude the use of CRT in patients with permanent atrial fibrillation, although small series suggest a benefit of the therapy in these patients. The role of cardiac imaging with echocardiography to detect cardiac dyssynchrony promises to improve patient selection by not only excluding likely nonresponders, but also extending the therapy to those with dyssynchrony in the absence of QRS prolongation. Expanded indications under evaluation include the role of CRT in patients with mildly symptomatic CHF, mild to moderate LV dysfunction, dyssynchrony in the absence of QRS prolongation, and dyssynchrony induced by right ventricular pacing.

Anomalous origin of the coronary arteries from the pulmonary trunk in two separate patients with a review of the clinical implications and current treatment recommendations.

Anomalous origin of a coronary artery from the pulmonary artery (PA) is an unusual abnormality. These anomalies are often hemodynamically significant and can lead to myocardial ischemia, myocardial infarction, and sudden cardiac death. Anomalous origin of the left coronary artery (LCA) from the pulmonary trunk is known as Bland-White-Garland syndrome and causes death in 80% to 85% of affected children in the first year of life. Treatment of the LCA arising from the PA is typically surgical, with ligation and reimplantation of the LCA to the aorta. In contrast, origination of the right coronary artery from the PA is usually a benign anomaly, although clinically significant sequelae can develop. Controversy exists regarding the need to intervene in the cases of patients with this usually incidentally discovered anomaly. We review the clinical presentation and treatment of patients with each anomaly and the current recommendations regarding the clinical course and management of such patients.

Vascular effects of sildenafil in hypertensive cardiac transplant recipients.

BACKGROUND: Sildenafil is commonly used in the treatment of erectile dysfunction in hypertensive male cardiac transplant recipients (CTR); however, little is known about the vascular effects of sildenafil in these patients. METHODS: Central and peripheral arterial blood pressure (BP), heart rate, and brachial artery reactivity were determined in 15 hypertensive male CTR before and after oral sildenafil (50 mg) administration. RESULTS: Sildenafil improved brachial and aortic systolic BP, pulse pressure, aortic augmentation index, left ventricular tension time index, travel time of the reflected aortic pressure wave, and brachial artery reactivity (P <.01 for each comparison). No patient became hypotensive with sildenafil despite continuation of usual antihypertensive medications. CONCLUSIONS: Sildenafil (50 mg) is well tolerated in hypertensive CTR and improves BP, aortic augmentation index, and endothelial function. By decreasing the amplitude of the reflected pressure wave and delaying its return to the heart, sildenafil reduces left ventricular afterload and systolic stress.

Amplitude and timing of central aortic pressure wave reflections in heart transplant recipients.

BACKGROUND: Hypertension (HTN) assessed by sphygmomanometer is a common finding in heart transplant recipients (HTR); however, little is known about the contribution of arterial wave reflection to central aortic pressure in these patients. The aim of this study was to measure the central aortic pressure wave in HTR on antihypertensive therapy and determine the effects of amplitude and timing of wave reflection on the various components of the wave. METHODS: A total of 53 stable adult HTR on antihypertensive medication underwent brachial artery blood pressure ([BP]; by sphygmomanometry) and central aortic pressure (by noninvasive radial artery applanation tonometry and use of a generalized transfer function) measurements at rest. Central aortic augmentation index (Ala), an indicator of arterial stiffness, was calculated from the aortic pressure waveform. Patients were divided into three groups (A, B, and C) based on the amplitude of AIa. RESULTS: Mean brachial BP was 136 +/- 15/84 +/- 9.4 mm Hg. Group A patients (n = 25) had a higher AIa (average 21% +/- 7.6%) than group B (n = 18, AIa = 6.5% +/- 3.0%, P < .001) or group C (n = 10, AIa = -8.7% +/- 8.1%, P < .001) patients. The amplitude of AIa was inversely related to the travel time (delta(t)p/2) of the reflected pressure wave from the periphery to the heart (r = -0.78, P < .001). Despite this clear stratification of patients by aortic pulse wave analysis, standard cuff pressure was similar among the groups. CONCLUSIONS: Noninvasive analysis of the central aortic PRESSURE wave identified a subgroup of hypertensive HTR with increased arterial stiffness, increased propagation of the reflected wave, and augmented aortic systolic and pulse pressure not identified with the sphygmomanometer.