Reddy, S

Abstract Rationale Septic shock patients require vasopressors to maintain adequate mean arterial pressure (MAP). The 2021 Surviving Sepsis Campaign Guideline recommends norepinephrine (NE) as first line, followed by vasopressin (VP). Early NE initiation is associated with faster achievement of MAP goals, lower fluid requirements, increased PaO2/FiO2 ratio, more mechanical-free ventilation days, and lower mortality. However, higher NE dosages can cause excessive vasoconstriction, impaired perfusion, lower Pa/Fi ratios, and increase in-hospital mortality. We tested the association between timing and cumulative dose of the NE with PaO2/FiO2 ratio, duration of invasive mechanical ventilation (IMV) and hospital length of stay (LOS). Methods We conducted a retrospective cohort analysis of adult septic shock patients treated with NE at Mayo Clinic Rochester Medical ICU between January 3, 2006, and April 17, 2018. Patients receiving other initial vasopressors were excluded. We developed linear regression models to assess how NE initiation time, defined as hours from sepsis identification, and cumulative dose, defined as total NE administered during ICU stay, affected median PaO2/FiO2 ratio, duration of IMV, and hospital LOS. We assessed for associations using: 1) an unadjusted model; 2) an adjusted model for baseline demographics and comorbidities (age, sex, weight, and Charlson Comorbidity Index); 3) an adjusted model for illness severity on day 1, using APACHE III and SOFA scores. Results Of 1,082 patients, 70% (n = 759) started NE as initial vasopressor. Timing of NE initiation was independently linked to shorter IMV and hospital LOS, but not to PaO2/FiO2 ratio. Across all models, earlier NE use significantly reduced IMV duration (β over 1.3992 ± 0.11 and p < 0.0001) and hospital LOS (average β 0.067 ± 0.01 and p < 0.0001). In contrast, a higher cumulative NE dose during the ICU stay was associated with a lower median PaO2/FiO2 ratio (β: -0.0053 ± 0.002, p = 0.0061), and remained significant in the adjusted models (β -0.0065 ± 0.002, p = 0.0013; and β -0.005 ± 0.002, p = 0.0132). Additionally, higher NE doses were significantly associated with longer IMV duration and hospital LOS in all models with p < 0.0001. Conclusion Although earlier initiation of vasopressor support with NE is associated with shorter durations of IMV and hospital LOS, higher cumulative doses are linked to the opposite effect. Increased NE doses were associated with lower PaO2/FiO2 ratios, delayed extubation and prolonged hospitalization. These findings highlight the importance of early NE administration and careful dose titration to optimize patient recovery. This abstract is funded by: None

Abstract Rationale Hypophosphatemia affects about one-third of intensive care unit (ICU) patients and is linked to longer hospital stays, illness severity and poor outcomes, yet guidelines for monitoring and correction remain unclear. Studies show a strong association between hypophosphatemia and both prolonged invasive mechanical ventilation (IMV) and weaning failure in patients with respiratory failure, due to reduced adenosine triphosphate generation and weakened respiratory muscle performance. Although phosphate abnormalities correlate with higher mortality in sepsis and septic shock, their impact on IMV duration in this population remains unclear. Therefore, we aimed to evaluate the independent association between hypophosphatemia during ICU stay and the duration of IMV in patients with septic shock. Methods We studied adult patients with septic shock admitted to the medical ICU at Mayo Clinic, Rochester, between March 1, 2006, and April 17, 2018. A retrospective analysis was conducted to examine the association between hypophosphatemia—defined as any serum phosphate level < 2.5 mg/dL during the ICU stay—and the duration of IMV in hours. The following linear regression models were used: 1, unadjusted; 2, adjusted for baseline demographics (age, sex, weight); 3, adjusted for baseline respiratory comorbidities and Charlson Comorbidity Index (CCI); and 4, adjusted for illness severity (using APACHE III and SOFA scores) and oxygenation (minimum PaO2/FiO2 score during ICU stay). For each model, the β-coefficient was reported, which represents additional hours of IMV associated with hypophosphatemia, along with 95% confidence intervals and p-values. Results The study included 1082 patients, among them 653 (60.4%) required IMV. 53.6% (n = 350) developed hypophosphatemia during their ICU stay. The mean duration of IMV was significantly longer in patients with hypophosphatemia compared with those without (184 ± 218 h vs 100 ± 126 h; p < 0.001; 95% CI 56-112). This association persisted across all multivariable linear regression models. After adjustment for baseline demographics, hypophosphatemia remained significantly associated with longer IMV duration (β = 79.8 h; 95% CI 51.8-107.8; p < 0.001). Further adjustment for respiratory comorbidities and CCI yielded similar results (β = 81.8 h; 95% CI 54.2-109.4; p < 0.001). After controlling for illness severity and oxygenation status, hypophosphatemia remained independently associated with prolonged IMV duration (β = 69.2 h; 95% CI 39.9-98.4; p < 0.001). Conclusion Hypophosphatemia was independently associated with longer duration of IMV in patients with septic shock, which prolongs ICU level care and delays rehabilitation. This highlights the need for updates on guidelines for maintaining optimal serum phosphate levels in patients who are mechanically ventilated. This abstract is funded by: None