Discordance Between Respiratory Drive and Sedation Depth in Critically Ill Patients Receiving Mechanical Ventilation.

OBJECTIVES: In mechanically ventilated patients, deep sedation is often assumed to induce "respirolysis," that is, lyse spontaneous respiratory effort, whereas light sedation is often assumed to preserve spontaneous effort. This study was conducted to determine validity of these common assumptions, evaluating the association of respiratory drive with sedation depth and ventilator-free days in acute respiratory failure. DESIGN: Prospective cohort study. SETTING: Patients were enrolled during 2 month-long periods in 2016-2017 from five ICUs representing medical, surgical, and cardiac specialties at a U.S. academic hospital. PATIENTS: Eligible patients were critically ill adults receiving invasive ventilation initiated no more than 36 hours before enrollment. Patients with neuromuscular disease compromising respiratory function or expiratory flow limitation were excluded. INTERVENTIONS: Respiratory drive was measured via P0.1, the change in airway pressure during a 0.1-second airway occlusion at initiation of patient inspiratory effort, every 12 ± 3 hours for 3 days. Sedation depth was evaluated via the Richmond Agitation-Sedation Scale. Analyses evaluated the association of P0.1 with Richmond Agitation-Sedation Scale (primary outcome) and ventilator-free days. MEASUREMENTS AND MAIN RESULTS: Fifty-six patients undergoing 197 bedside evaluations across five ICUs were included. P0.1 ranged between 0 and 13.3 cm H2O (median [interquartile range], 0.1 cm H2O [0.0-1.3 cm H2O]). P0.1 was not significantly correlated with the Richmond Agitation-Sedation Scale (RSpearman, 0.02; 95% CI, -0.12 to 0.16; p = 0.80). Considering P0.1 terciles (range less than 0.2, 0.2-1.0, and greater than 1.0 cm H2O), patients in the middle tercile had significantly more ventilator-free days than the lowest tercile (incidence rate ratio, 0.78; 95% CI, 0.65-0.93; p < 0.01) or highest tercile (incidence rate ratio, 0.58; 95% CI, 0.48-0.70; p < 0.01). CONCLUSIONS: Sedation depth is not a reliable marker of respiratory drive during critical illness. Respiratory drive can be low, moderate, or high across the range of routinely targeted sedation depth.

A multicenter retrospective study evaluating the impact of desmopressin on hematoma expansion in patients with antiplatelet-associated intracranial hemorrhage.

INTRODUCTION: Antiplatelet medications interfere with hemostasis which can contribute to increased risk of hematoma expansion and potentially worse outcomes in patients presenting with intracranial hemorrhages (ICH). Current Neurocritical Care Society guidelines recommend desmopressin (DDAVP) in patients with antiplatelet-associated ICH with evidence limited by small cohorts. MATERIALS AND METHODS: Patients were included in our multi-center, retrospective study if they had computed tomographic (CT) scan confirmed ICH and were taking antiplatelet medications. Patients were excluded if hospital length of stay was <24 h, administered DDAVP dose was <0.3 µg/kg, no follow-up head CT scan was performed within the first 24 h after baseline, major neurosurgical intervention was performed in between CT scans, or the injury was an acute on chronic ICH. The primary outcome was incidence of hematoma expansion (defined as >20 % increase from baseline). Secondary outcomes were incidence of thrombotic complications within 7 days, largest absolute decrease in serum sodium within the first 24 h, and patient disposition. RESULTS: Among the 209 patients included in the study, 118 patients received DDAVP while 91 did not. The frequency of hematoma expansion was similar between patients who received DDAVP and those who did not (16.1 % vs 17.6 %; P = 0.78). No difference in secondary outcomes was observed between the two groups. CONCLUSIONS: These findings in conjunction with recently published literature may suggest minimal benefit or harm with DDAVP treatment. However, further study could elucidate any potential impact on long-term function outcomes.

Dexmedetomidine as add-on sedation to reduce continuous infusion sedative use in mechanically ventilated patients.

PURPOSE: To characterize the impact of add-on dexmedetomidine therapy on baseline continuous infusion sedative use. METHODS: A retrospective, single-center, chart review-based study was conducted to assess outcomes of and potential predictors of response to add-on dexmedetomidine therapy in mechanically ventilated intensive care unit (ICU) patients who were already receiving continuous infusions of sedatives. Patients were defined as complete, partial, or nonresponders to add-on dexmedetomidine therapy if initial sedative infusion rates were reduced by 100%, by 50% to 99%, and by less than 50%, respectively, at 6 and 24 hours after initiation of dexmedetomidine. RESULTS: Among the 100 patients included in the study sample, there were 54 complete responders, 21 partial responders, and 25 nonresponders to dexmedetomidine add-on therapy at 6 hours after dexmedetomidine initiation; at 24 hours, there were 65 complete and 12 partial responders and 23 nonresponders. Of the variables tested (ie, baseline characteristics, opioid and antipsychotic use, hemodynamic parameters), none differentiated between complete or partial responders and nonresponders. Ventilator time, ICU length of stay (LOS), and hospital LOS after add-on dexmedetomidine therapy initiation were shorter among both partial responders and complete responders vs nonresponders (median, 1.1 days vs 4.1 days [P = 0.01], 7.0 days vs 14.1 days [P = 0.20], and 11.0 vs 17.0 days [P = 0.58], respectively), with only ventilator time being significantly different. CONCLUSION: Add-on dexmedetomidine therapy can obviate or reduce the need for alternate sedation in as many as 75% of mechanically ventilated ICU patients. However, the addition of dexmedetomidine does not allow the reduction of alternate sedation in a substantial minority of patients, and failure to respond to dexmedetomidine can be identified as early at 6 hours after add-on therapy initiation. In the absence of clear predictors of response to dexmedetomidine, these data suggest empiric trials of dexmedetomidine can be considered but should be time-limited.

Survey of Nurses' Experiences Applying The Joint Commission's Medication Management Titration Standards.

BACKGROUND: Critical care nurses titrate continuous infusions of medications to achieve clinical end points. In 2017, The Joint Commission (TJC) placed restrictions on titration practice, decreasing nurses' autonomous decision-making. OBJECTIVES: To describe the practice and perceptions of nurses regarding the 2017 TJC accreditation/regulatory standards for titration of continuous medication infusions. METHODS: A survey of nurses' experiences titrating continuous medication infusions was developed, validated, and distributed electronically to members of the American Association of Critical-Care Nurses. RESULTS: The content validity index for the survey was 1.0 for relevance and 0.95 for clarity. A total of 781 nurses completed the survey; 625 (80%) perceived titration standards to cause delays in patient care, and 726 (93%) experienced moral distress (mean [SD], 4.97 [2.67]; scale, 0-10). Among respondents, 33% could not comply with titration orders, 68% reported suboptimal care resulting from pressure to comply with orders, 70% deviated from orders to meet patient needs, and 84% requested revised orders to ensure compliance. Suboptimal care and delays in care significantly and strongly (regression coefficients ≥0.69) predicted moral distress. CONCLUSIONS: Critical care nurses perceive TJC medication titration standards to adversely impact patient care and contribute to moral distress. The improved 2020 updates to the standards do not address delays and inability to comply with orders, leading to moral distress. Advocacy is indicated in order to mitigate unintended consequences of TJC medication management titration standards.

Characteristics of Hospitalized Patients Screening Positive for Delirium.

BACKGROUND: Delirium in the hospitals leads to worse outcomes for patients. There were no previous studies that characterize patients with delirium from multiple hospital locations. OBJECTIVE: To describe patient characteristics screening positive for delirium and identify any correlations with hospital location and medication use. DESIGN, SETTINGS, PATIENTS: Retrospective chart review of 227 hospitalized patients from a large, academic, tertiary referral, 2-campus health system. Patients were ≥18 years old and had delirium for at least ≥24 hours. Validated delirium screening tools were utilized. MEASUREMENTS: Patients' demographics, inpatient stay information, delirium episodes characteristics, drugs, and palliative and psychiatry teams' involvement. RESULTS: Most patients were older with a mean age of 64.1 years. The most common primary diagnoses were infection, cardiac, and pulmonary. Average length of delirium was 7.2 days (standard deviation [SD] = 8.2), and average length of stay (LOS) was 18.7 days (median = 10.5, SD = 35.1, 95% confidence interval = 14.1-23). Thirty-day readmission rate was 24.8% (65/262 hospitalizations); 12.8% of patients died in the hospital (29/227). Around one-third of hospitalizations had involvement of palliative care, palliative psychiatry, or general psychiatry team. There was a decrease in the number of medications administered 24 hours after the first recording of delirium compared to the immediate preceding 48 hours. Those hospitalizations where delirium first occurred in the intensive care unit (ICU) did have a longer LOS (average = 22.9, SD = 45.7) than those where delirium first occurred outside the ICU (average = 14.8, SD = 20.5). Patients were likely to have received an opioid within 48 hours in 51% of hospitalizations and to have received benzodiazepines in 16% of hospitalizations. CONCLUSION: In our study, we found that delirium significantly impacted length of delirium episode, number of episodes of delirium, length of hospital admission, and mortality. The population most sensitive to the impacts of delirium were elderly patients.

Four-Factor Prothrombin Complex Concentrate for Coagulopathy Reversal in Patients With Liver Disease.

A 4-factor prothrombin complex concentrate (4F-PCC, Kcentra®) was recently approved in the United States for the reversal of vitamin K antagonist-associated major bleeding, but it is often used to reverse coagulopathy in patients with liver disease (LD). This single-center, retrospective study analyzed the efficacy and safety of 4F-PCC administered in patients with and without LD. Prothrombin time/International Normalized Ratio (PT/INR) reversal with 4F-PCC was attempted in 85 patients; LD was documented in 31 patients. Coagulopathy reversal and hemostasis with 4F-PCC were inferior in patients with LD compared to patients without LD. Coagulopathy reversal, defined as INR = 1.5 after 4F-PCC administration, was achieved in 6 (19.4%) LD patients, compared to 44 (81.5%) non-LD patients ( p < 0.01). Hemostasis was achieved in 6 LD patients (19.4%) compared to 23 non-LD patients (42.6%) ( p = 0.03). Thromboembolic events occurred in 1 LD patient (3.2%) and 8 non-LD patients (14.8%) ( p = 0.15). Mortality was 51.6% in LD patients and 18.5% in non-LD patients ( p < 0.01). These observations suggest that the efficacy of 4F-PCC is suboptimal to correct coagulopathy and hemostasis in patients with LD, who have high rates of in-hospital mortality due to sequelae of LD. The incidence of thromboembolic events appeared comparable, suggesting that 4F-PCC does not cause undue thromboembolism in LD patients. In conclusion, 4F-PCC appears to be safe in LD patients when administered judiciously; however, further studies are necessary to optimize its use and elucidate its hemostatic potential in this patient population.

Saccharomyces cerevisiae RRM3, a 5' to 3' DNA helicase, physically interacts with proliferating cell nuclear antigen.

Proliferating cell nuclear antigen (PCNA) plays an essential role in eukaryotic DNA replication, and numerous DNA replication proteins have been found to interact with PCNA through a conserved eight-amino acid motif called the PIP-box. We have searched the genome of the yeast Saccharomyces cerevisiae for open reading frames that encode proteins with putative PIP-boxes and initiated testing of 135 novel candidates for their ability to interact with PCNA-conjugated agarose beads. The first new PCNA-binding protein identified in this manner is the 5' to 3' DNA helicase RRM3. Yeast two-hybrid tests show that N-terminal deletions of RRM3, which remove the PIP-box but leave the helicase motifs intact, abolish the interaction with PCNA. In addition, mutating the two phenylalanine residues in the PIP-box to alanine or aspartic acid reduces binding to PCNA, confirming that the PIP-box in RRM3 is responsible for interaction with PCNA. The results presented here suggest that the RRM3 helicase functions at the replication fork.