During hemorrhagic shock, blood loss causes a fall in blood pressure, decreases cardiac output, and, consequently, O₂ transport. The current guidelines recommend the administration of vasopressors in addition to fluids to maintain arterial pressure when life-threatening hypotension occurs in order to prevent the risk of organ failure, especially acute kidney injury. However, different vasopressors exert variable effects on the kidney, depending on the nature and dose of the substance chosen as follows: Norepinephrine increases mean arterial pressure both via its α-1-mediated vasoconstriction leading to increased systemic vascular resistance and its β1-related increase in cardiac output. Vasopressin, through activation of V1-a receptors, induces vasoconstriction, thus increasing mean arterial pressure. In addition, these vasopressors have the following different effects on renal hemodynamics: Norepinephrine constricts both the afferent and efferent arterioles, whereas vasopressin exerts its vasoconstrictor properties mainly on the efferent arteriole. Therefore, this narrative review discusses the current knowledge of the renal hemodynamic effects of norepinephrine and vasopressin during hemorrhagic shock.

Background: Capillary refill time (CRT) has been suggested as a variable to follow during the course of septic shock. We systematically investigated the effects on CRT of volume expansion and norepinephrine. Methods: In 69 septic shock patients, we recorded mean arterial pressure (MAP), cardiac index (CI), and 5 consecutive CRT measurements (video method, standardized pressure applied on the fingertip) before and after a 500-mL saline infusion in 33 patients and before and after an increase of the norepinephrine dose in 36 different patients. Fluid responders were defined by an increase in CI ≥ 15%, and norepinephrine responders by an increase in MAP ≥ 15%. Results: The least significant change of CRT was 23%, so that changes in CRT were considered significant if larger than 23%. With volume expansion, CRT remained unchanged on average in patients with baseline CRT < 3 s (n = 7) and in all but one patient with baseline CRT ≥ 3 s in whom fluid increased CI < 15% (n = 13 “fluid non-responders”). In fluid responders with baseline CRT ≥ 3 s (n = 13), CRT decreased in 8 patients and remained unchanged in the others, exhibiting a dissociation between CI and CRT responses. The proportion of patients included > 24 h after starting norepinephrine was higher in patients with such a dissociation than in the other ones (60% vs. 0%, respectively). Norepinephrine did not change CRT significantly (except in one patient) if baseline CRT was ≥ 3 s and the increase in MAP < 15% (n = 6). In norepinephrine responders with prolonged baseline CRT (n = 11), it increased in 4 patients and remained unchanged in the other ones, which exhibited a dissociation between MAP and CRT responses. Conclusions: In septic shock patients with prolonged CRT, CRT very rarely improves with treatment when volume expansion increases cardiac output < 15% and increasing norepinephrine increases MAP < 15%. When the effects of fluid infusion on cardiac output and of norepinephrine on MAP are significant, the response of CRT is variable, as it decreases in some patients and remains stable in others which exhibit a dissociation between changes in macrohemodynamic variables and in CRT. In this regard, CRT behaves as a marker of microcirculation. Trial registration: ClinicalTrial.gov (NCT04870892). Registered January15, 2021. Ethics committee approval CE SRLF 21-25.

In patients with septic shock as well as in the critically ill, the impact of hypothermia and core temperature changes during the first 24 h on mortality remains uncertain. In this post-hoc analysis of the SEPSISPAM trial, we investigated the association between hypothermia at inclusion, hypothermia trajectories and 90-day mortality in patients with septic shock. This post-hoc analysis of the SEPSISPAM trial included patients with septic shock enrolled within 6 h of vasopressors initiation. Core temperature was assessed every 2 h during the first 24 h. Hypothermia was defined by a temperature <36 °C. Mortality was assessed at day 90. We included 691 patients from the SEPSISPAM trial, of whom 103 (14.9%) presented with hypothermia at inclusion. After adjustment for confounding factors, as compared with patients without hypothermia at inclusion, patients with hypothermia at inclusion had a higher mortality (HR 1.92, 95% CI [1.38–2.67], p < 0.001). Three groups of patients were identified according to the evolution of their core temperature: “without hypothermia” (86.6%), i.e., patients without any hypothermia during the first 24 h; “transient hypothermia” (10%), i.e., patients with hypothermia at inclusion and becoming normothermic during the first 24 h, and “persistent hypothermia” (3.4%), i.e., patients with sustained hypothermia both at inclusion and during the first 24 h. Compared with patients without hypothermia, the “persistent hypothermia” group had the highest mortality rate at day 90 (78.3%, HR 2.83 [1.62−4.95], p < 0.0001). Mortality at day 90 increased according to temperature trajectories, being highest in patients with persistent hypothermia (78%), followed by those with transient hypothermia (49%), and lowest in patients without hypothermia (40%). In patients with septic shock, hypothermia at inclusion and persistence of hypothermia during the first 24 h were associated with higher mortality at day 90. Mortality increased according to the course of hypothermia during the first 24 h, being highest in patients with persistent hypothermia, followed by those with transient hypothermia, and lowest in patients who never developed hypothermia.

OBJECTIVES: Guidelines recommend targeting a mean arterial pressure (MAP) greater than or equal to 65 mm Hg in septic shock. Although experts advocate for individualized targets, no validated bedside tool exists. An increased renal resistive index (RRI) is associated with acute kidney injury, and increasing MAP can reduce RRI. This study investigated the physiologic impact of a higher MAP on renal function based on RRI evolution during a transient high MAP target test. DESIGN: Prospective physiologic and randomized study. SETTING: Medical ICU of a university hospital. Patients: Patients in the early phase of septic shock (norepinephrine ≥ 0.05 µg/kg/min base within 9 hr of initiation, with or without lactate > 2 mmol/L) without chronic kidney disease or immediate need for renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients underwent a standardized 2-hour MAP test (65–70 followed by 80–85 mm Hg) with RRI measured at each period. RRI responders were defined by an RRI decrease greater than or equal to 0.05 during the MAP test. Following the MAP test, patients were randomized according to the “low” (65–70) or “high” (80–85 mm Hg) MAP target for 5 days, stratified by RRI response during the MAP test. Eighty patients were randomized; 23 (29%) were RRI responders. Among RRI responders, the higher MAP target was not associated with improved renal outcomes (i.e., diuresis, Kidney Disease: Improving Global Outcomes stage, need for renal replacement therapy, or serum creatinine). RRI nonresponders had higher urine output with a high MAP target, whereas no other renal parameter differed significantly; these findings should be considered exploratory. CONCLUSIONS: In early septic shock, a decrease in RRI during a MAP test did not identify patients who would benefit from higher MAP targets to improve renal function. Conversely, the absence of an RRI decrease during the MAP test may help identify patients in whom increasing MAP is associated with increased urine output.