Resuscitation Targets, Fluids, and Vasoactives in Septic Shock

Synopsis/abstract

Intravenous fluids and vasoactive medications represent the foundation of hemodynamic resuscitation for septic shock. Based on current evidence, initial fluid resuscitation of roughly 30 ml/kg with balanced crystalloids is reasonable for most patients. Carefully-monitored peripheral vein administration of the first-line vasopressor, norepinephrine, appears safe. Ongoing multimodal assessment and therapy titration integrating blood pressure, lactate clearance, capillary refill time, and dynamic measures of fluid responsiveness has outcomes equivalent to protocolized goal-directed resuscitation. However, better evidence is urgently needed for many common septic shock management issues.

Introduction

Sepsis and septic shock are not fixed sequalae of severe infection, but instead are the consequences of a maladaptive host response to infection, Compared to other shock states, the management of septic shock is therefore the most complicated and least amenable to resolution via interventions targeting the underlying trigger.¹ This review will discuss current evidence guiding the hemodynamic resuscitation of septic shock using intravenous (IV) fluids and vasoactive medications, highlighting potential opportunities to personalize treatments and targets for resuscitation.

Resuscitation Targets

Current septic shock therapies primarily target the syndrome’s macrocirculatory mechanisms, including vasoplegia, hypovolemia due to blood pooling in capacitance vessels and capillary leakage from endothelial injury, and myocardial dysfunction. However, microvascular dysfunction from glycocalyx disruption, decreased capillary density, microvascular thrombosis, heterogenous capillary blood flow, and tissue hypoxia contributes to macrovascular dysfunction, independently drives sepsis-related tissue damage,² and may persist after macrovascular function normalizes (a phenomenon known as hemodynamic incoherence).³ While microcirculatory resuscitation is a promising area for future individualized care in sepsis, however, there are currently no evidence-based therapies targeting sepsis-induced microvascular dysfunction or hemodynamic incoherence^4,5,6 and advanced techniques for microcirculatory monitoring have not achieved routine bedside availability or application.

Blood pressure

Adequate mean arterial pressure (MAP) is essential to maintain cardiac output (CO), venous return, and oxygen delivery (DO₂). MAP’s association with clinical outcomes is stronger than systolic or diastolic arterial pressures, though emerging evidence suggests diastolic pressures may provide useful prognostic information.^7,8,9 Autoregulation of perfusion to the brain, heart, and kidneys declines around a MAP of 60 mmHg, as does perfusion pressure for other organs.¹⁰

The 2021 Surviving Sepsis Campaign (SSC) strongly recommends targeting a MAP of 65 mmHg (Table 1),¹¹ but the evidence to support this target is based largely on physiologic principles, observational data, and tradition rather than rigorous trial data.^12,13,14 The 2014 SEPSISPAM trial found similar mortality but greater catecholamine exposure and higher rates of atrial fibrillation for patients randomized to a target MAP of 80–85 mm Hg compared to 65–70 mm Hg.¹⁵ However, subgroup analysis demonstrated reduced renal replacement therapy (RRT) in the higher MAP group for patients with chronic hypertension. After a 2016 pilot trial suggested increased mortality with higher MAP in patients over 75,¹⁶ the 65 trial (2020) compared “permissive hypotension” (MAP 60–65 mm Hg) to standard care in patients 65 years or older. As with the SEPSISPAM trial, both treatment arms overshot their MAP targets, and permissive hypotension did not affect 90-day mortality or RRT requirements.¹⁷ Overall, with mixed results from meta-analyses^18,19 and trials that have consistently delivered blood pressures above goals, the optimal MAP target in septic shock remains an open question.

Table 1.

Key recommendations from 2021 Surviving Sepsis Campaign guidelines.^*

Category	Recommendation	Recommendation strength	Quality of evidence
Resuscitation targets	Target MAP ≥65 mmHg	Strong	Moderate
	Use dynamic measures over physical examination or static parameters to guide fluid resuscitation	Weak	Very low
	Employ lactate clearance to guide resuscitation, and use capillary refill time as an adjunct	Weak	Low
IV fluid	Administer ≥30 ml/kg IV fluid to patients with hypoperfusion within 3 hours of starting resuscitation	Weak	Low
	Crystalloid fluids are first choice for fluid resuscitation	Strong	Moderate
	Use balanced crystalloids in preference to	Weak	Low
	Strictly avoid starch-based resuscitation fluids	Strong	High
	Add albumin for patients receive large-volume fluid resuscitation	Weak	Moderate
Vasopressors	Employ norepinephrine as the first-line vasopressor, especially in preference to dopamine	Strong	Mixed†
	Add vasopressin for patients with “inadequate” MAP on norepinephrine	Weak	Moderate
	Add epinephrine for patients with “inadequate” MAP on norepinephrine and vasopressin	Weak	Low
	Use epinephrine or add dobutamine to norepinephrine for patients with cardiac dysfunction and hypoperfusion despite adequate MAP and fluid resuscitation	Weak	Low

Abbreviations: IV, intravenous; MAP, mean arterial pressure.

^*Adapted from Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med 2021;49:e1063–e1143.¹¹

^†Strength of evidence for comparison of first-line norepinephrine to alternative vasopressors: dopamine – high; vasopressin – moderate; epinephrine – low; selepressin – low; angiotensin II – very low.

Mixed venous oxygen saturation

The utility of mixed venous oxygen saturation (SvO₂) is physiologically rooted in the fact that the arterial-to-venous O2 difference (a-v O₂) correlates directly with oxygen consumption and indirectly with cardiac output. Assuming normal oxygen saturation and stable oxygen consumption, increased a-v O_2, or a low venous oxygen saturation, indicates a decrease in CO. However, impaired tissue oxygen uptake due to microcirculatory and mitochondrial/cellular dysfunction may lead to an elevated SvO₂ in septic patients with adequate CO, challenging the bedside application of SvO₂ assessment in septic shock.²⁰

Central venous oxygen (ScvO₂)-guided resuscitation was popularized in 2001 by Rivers et al., whose early goal directed therapy (EGDT) protocol targeted an ScvO₂ above 70% and substantially improved mortality in their seminal single-center trial.²¹ However, three large, multicenter trials — ProCESS, ARISE, and ProMISe — designed to compare EGDT to usual care in a multicenter, global setting subsequently found no difference in mortality with EGDT versus usual care despite increased IV fluid, vasoactives, and transfusions.^22,23,24,25 Consequently, SvO₂ monitoring is no longer recommended in international guidelines or core sepsis protocols, although it may still be useful for individual patients while recalling that a “normal” SvO₂ may reflect a combination of inadequate CO (driving SvO₂ down) and microcirculatory dysfunction (driving SvO₂ up).

Lactate

Lactate has secured a core role in sepsis resuscitation over the past two decades and is the only biomarker mentioned as a resuscitation target in the most recent SSC guidelines.^5,26,27 Early resuscitation strategies targeting a lactate clearance of 10–20% within 6–8 hours of admission decreased mortality in two randomized control trials (RCT) when compared to ScvO₂-guided resuscitation and standard of care.^28–32 Compared to cardiogenic or hemorrhagic shock, however, where there is a clear decrease in DO₂, lactate levels’ relationship with tissue hypoxia and anaerobic metabolism is complex in sepsis due to mechanisms including accelerated glycolysis, stimulation of anaerobic glycolysis by catecholamines, and decreased mitochondrial oxygen utilization.^33–35 As a result, lactate-guided resuscitation remains controversial. Clinicians using lactate to guide septic shock resuscitation should be aware that persistent lactate elevation may reflect sepsis-induced microvascular, cellular, and metabolic dysfunction and avoid unconsidered/reflexive fluid or vasoactive administration.

Since the highest lactate (and mortality) is observed at the low and high extremes of ScvO₂, there may be an opportunity to integrate these two parameters.³⁵ Lactic acidosis with concomitant low ScvO2 might indicate inadequate DO₂ for patients with low ScvO₂, warranting attempts at increasing CO. Conversely, lactic acidosis and high ScvO₂ might suggest a problem with oxygen utilization, supporting a more conservative approach to fluid management and vasoconstrictors.

Clinical signs of peripheral perfusion

Although strong supporting evidence is limited, clinicians frequently employ signs of peripheral perfusion amenable to bedside assessment such as skin exam, urine output, and mental status to steer bedside shock resuscitation. Because the persistence of microcirculatory dysfunction despite adequate MAP correlates with persistently elevated lactate levels and higher mortality,^36–38 capillary refill time (CRT) may be a particularly useful exam finding. CRT measurement allows rapid, convenient, and cheap bedside assessment of peripheral perfusion, but varying definitions of a “normal” CRT and inconsistent measurement methods have constrained CRT’s bedside application and interpretation.^37,39–43 Nevertheless, the ANDROMEDA SHOCK trial³⁹— which employed standardized CRT measurements and a 3-second cutoff to define abnormal CRT — found that a resuscitation strategy guided by CRT outperformed one targeting lactate clearance, with less organ failure at 72 hours and potentially lower 28-day mortality (HR 0.75, 95% CI 0.55–1.02). Whether the structured CRT-directed resuscitation strategy outperforms usual care, however, is unknown, but CRT was nevertheless added to the latest international sepsis management guidelines (Table 1)..

While the physiology underlying skin mottling is similar to CRT and a five-point grading scale for mottling is predictive of 14-day mortality independent of vasopressor dose,^38,44 evidence for its clinical application to guide resuscitation is lacking.

Other potential targets

Near-infrared spectroscopy (NIRS) enables direct measurement of tissue oxygen hemoglobin saturation (StO₂), which correlates inversely with both ScvO₂ and mortality in septic shock.^45–47 Dynamic evaluation of the speed with which StO2 values recover after transient occlusion of arterial supply is a potential direct measure of microcirculatory function. However, neither static nor dynamic NIRS-derived StO₂ measurement has been systematically tested as a resuscitation target.

Visualization of the sublingual microcirculation with polarized light or darkfield microscopy reveals reduced microvascular density, heterogeneity of blood flow, and intermittently perfused vessels in sepsis, changes that resolve in survivors while persisting in non-survivors.^48,49 However, a recent randomized trial found clinical teams provided darkfield microscopy data made more changes in vasoactive therapy and administered more IV fluids to patients with shock without influencing either microcirculatory parameters at 24 hours or mortality.⁶

Fluids

Rationale and modern history of fluid resuscitation in sepsis

Physiologically, fluid administration in sepsis is intended to reverse the negative effects of arterial and venous vasoplegia, vascular leak, and volume depletion on CO and DO2 in the septic patient and thereby increase tissue oxygenation. Whereas historic practice largely depended on these physiologic rationale,⁵⁰ the Rivers et al. trial in 2001 provided higher quality evidence for aggressive fluid resuscitation.²¹ Alongside the advent of the Surviving Sepsis Campaign,⁵¹ this trial began a period of liberal fluid resuscitation, often 5L or more, during early sepsis care. By the time the international ProCESS, ARISE, and ProMISe trials comparing EGDT to usual care were enrolling from 2008–2014, early, aggressive fluid resuscitation was routine in septic shock. As a result, patients in the comparator (usual care) arms of these three ultimately negative trials received far more fluid than the usual care patients in the original Rivers et al. trial’s and nearly as much fluid as that trial’s EGDT patients.^22–24 While these ultimately negative trials were ongoing, however, observational data — certainly vulnerable to residual confounding by indication despite efforts at adjustment — emerged suggesting increased mortality, prolonged length of stay, decreased ventilator-free days, and worse AKI with positive fluid balance and a potential benefit from prompt fluid removal (“deresuscitation”). In addition,^52–54 trials published in 2011 and 2014 that enrolled patients in Africa with sepsis — low-resource settings with limited access to mechanical ventilation — demonstrated increased mortality among patients assigned to early, aggressive fluid resuscitation.^56,57 Together with the negative results from the EGDT trials, these trials and observational data helped launch the present era of fluid resuscitation practice characterized by a more conservative and individualized approach to fluid resuscitation.

Trials of restrictive fluids

To date, no trial has directly assessed a liberal versus conservative/restrictive fluid strategy for sepsis beginning from first presentation to care. The responsiveness of patients with sepsis to ongoing fluid resuscitation decreases rapidly during their early resuscitation,³⁹ however, and two recent major trials have compared these strategies beginning slightly later in their hospital course. First, the 2022 CLASSIC trial randomized patients with septic shock on vasopressors to a restrictive fluid protocol (250–500 mL IV fluid only if severe hypotension, mottling, lactate elevation, or oliguria) or usual care after their initial fluid resuscitation (around 3L). Liberal arm patients received more IV fluids than those in the restrictive arm (1.3L vs 0.5L on day 1), but there was no difference between the two groups in 90-day mortality, secondary outcomes (end-organ ischemia, AKI), and safety. By comparison, the CLOVERS trial randomized patients with sepsis-induced hypotension after 1–3L of initial fluid resuscitation (median 2.0L) to a 24-hour liberal (fluid-first) strategy or a restrictive (vasopressor-first) fluid strategy.⁵⁹ Median IV fluid in the liberal arm was 3.4L at 24 hours compared to 1.3L in the restrictive arm, but again there no between-strategy differences in mortality, safety, or secondary outcomes. While these neutral findings support the concept that resuscitation needs to be individualized to optimize patient outcomes, future research on heterogeneity of resuscitation treatment effect is needed to determine the targets and methods for such individualization, including which patients are most likely to benefit from a restrictive strategy and which may respond more favorably to a liberal approach.

Fluid responsiveness

The integration of “fluid responsiveness” assessment into septic shock clinical care has proceeded slowly since the concept’s emergence in the 1980s.^60,61 Factors impeding adoption include clinicians failing to see IV fluids as medications with both risks and benefits; dissemination of the “responsibility” for the risks of IV fluid resuscitation across numerous independent decisions points; guidelines and regulatory mandates that favor a standardized rather than personalized approach to fluid administration; and the fact that relatively easy-to-acquire static measures like the CVP and IVC diameter are insufficient to guide fluid management.^62–64

Dynamic assessment provides a much more meaningful assessment of fluid responsiveness than static measures. The most direct dynamic measure is an actual fluid challenge (300–500 mL) evaluated against the CO change calculated via a pulmonary artery catheter and considered positive if CO increased by ≥10–15%.⁶² However, given the goal of fluid responsiveness assessment is to avoid non-beneficial IV fluid and PA catheters are now rare in sepsis, clinicians now commonly employ dynamic assessment strategies that combine an alternative provocative maneuver simulating administration of fluid by increasing venous return with a response parameter assessing the maneuver’s effect on an estimated cardiac output or other surrogate measurement obtained via non-invasive or semi-invasive means (Table 2). The most important non-fluid provocative maneuver in routine use are:

• Passive leg raise (PLR): A semi-recumbent patient is repositioned in the supine position with legs raised to 30–45° to reversibly “auto-bolus” approximately 300ml of blood and thereby increasing mean systemic filling pressure and cardiac preload.^65,66 The PLR appears to be diagnostically accurate in several physiologic settings, irrespective of how it is measured.⁶⁷

• Respirophasic changes: Heart-lung interactions result in increased intrathoracic pressure during inhalation on positive pressure ventilation (or exhalation with spontaneous breathing), impeding venous return (preload) to the right heart and transiently reducing stroke volume and causing a drop in systolic blood pressure and pulse pressure. Cyclic fluctuations in CO, stroke volume and arterial pulse pressure over the respiratory cycle may be captured on an ongoing basis.⁶⁸ These assessments may be inaccurate in some physiologic conditions, including ARDS, assisted or spontaneous ventilation, among others.⁶²

Table 2.

Overview of dynamic assessment of fluid responsiveness.

Provocative maneuvers	Response parameters	Measurement method
Fluid challenge	Cardiac output (direct)	Invasive	Pulmonary artery catheter
Miniature fluid challenge	Cardiac output (estimated)
Passive leg raise	Pulse pressure variation	Semi-invasive	Thermodilution
Heart/lung interaction (positive pressure ventilation)	Stroke volume variation		Lithium dilution
Heart/lung interaction (spontaneous breathing)	Superior/inferior vena cava variation		Arterial pressure waveform
			Esophageal doppler
			Transesophageal echocardiography
		Non-invasive	Pulse pressure variation
			Arterial pressure waveform
			Bioimpedence
			Bioreactance
			Transthoracic echocardiography

While fluid responsiveness assessment is conceptually attractive, no large trials have demonstrated an impact on outcomes to support this approach.⁶⁹ Nevertheless, a recent multicenter phase 2 trial provided encouraging data, demonstrating significantly lower 72-hour fluid balance and less invasive mechanical ventilation and renal replacement therapy among patients randomized to fluid responsiveness assessment via PLR combined with bioreactance-based stroke volume assessment compared with usual care.⁷⁰

Fluid composition

Clinicians have four major choices for IV resuscitation fluids: normal saline, balanced crystalloids, albumin, or synthetic colloids. While the 2004 SAFE trial demonstrated no significant difference in 28-day mortality with 4% albumin instead of normal saline in ICU patients, only 18% of participants had sepsis.⁷¹ When, the ALBIOS trial revisited this question in 2014 in patients with sepsis,⁷² there was no difference in mortality with 20% albumin versus crystalloids, but a post-hoc analysis suggested a modest benefit in the subset of patients with septic shock. Around the same time, synthetic colloids such as hydroxyethyl starch (HES) were largely abandoned after trials demonstrated higher mortality and renal failure.^73,74

Normal saline contributes to hyperchloremic acidosis, and recent trials have compared this agent to balanced crystalloids (e.g., lactated Ringer’s). The SMART trial found that resuscitating ICU patients with balanced crystalloids reduced major adverse kidney events (death, renal replacement therapy, or persistent renal injury), especially for the subgroup of patients with sepsis. A secondary analysis focused on this group suggested nearly 5% lower mortality.⁷⁵ While subsequent RCTs failed to confirm a clear mortality benefit,^76,77 likely due to participants’ receipt of substantial normal saline resuscitation prior to enrollment, high-quality meta-analyses suggest a nearly 90% probability of benefit with using balanced crystalloid in sepsis.

Current guidelines and practice

While observational data suggest improved hospital mortality when utilizing early sepsis bundles as well as increased mortality in patients who did not receive 30ml/kg of fluid including populations at risk for volume overload (heart/renal failure),^78,79 this one-size-fits-all resuscitation strategy nevertheless remains controversial.⁸⁰ Current guidelines and performance metrics continue to advocate an initial resuscitation strategy of 30ml/kg, although the Surviving Sepsis Campaign downgraded their recommendation to “weak” in 2021 and supported using dynamic measures of fluid responsiveness to guide ongoing resuscitation (Table 1).^11,81 The 2025 guidelines on adult critical care ultrasound gave a conditional recommendation for using ultrasound to guide fluid status in patients with septic shock, based on meta-analysis demonstrating weak evidence in favor of improving clinical outcomes.⁸² The 2021 Surviving Sepsis guidelines also adopted a recommendation favoring balanced crystalloids over normal saline and continued strong recommendation against use of starch and weak recommendations to incorporate albumin-based resuscitation for patients receiving large fluid volumes (Table 1).¹¹

While deresuscitation is not yet part of these guidelines, clinicians are increasingly attentive to the risks of positive fluid balance and the potential benefits of deresuscitation.⁸³ Research addressing personalization of fluid resuscitation, heterogeneous response to fluid resuscitation across sepsis phenotypes, and deresuscitation timing and methods are urgent priorities.

Vasoactive medications

First-line vasopressor

Compared to the early 1990s, when dopamine was a preferred vasopressor in septic shock based on its perceived safety and the now debunked perception that it improved renal perfusion, norepinephrine is now clearly the preferred first-line vasopressor in septic shock.¹¹ This reflects evidence of increased septic shock mortality when hospitals were forced to administer other vasopressors during a U.S. national shortage of norepinephrine,⁸⁴ increased mortality and arrhythmias with dopamine⁸⁵ and epinephrine’s tendency to increase lactate and arrhythmias and impair gut perfusion.⁸⁶ While phenylephrine (a pure a₁ agonist) reduces heart rate in patients who develop atrial fibrillation while on norepinephrine⁸⁷ and should also be considered if patients exhibit dynamic outflow tract obstruction, phenylephrine’s utility must be balanced against the possibility of increased mortality when used in place of norepinephrine.⁸² However, norepinephrine may also have some immune suppressive properties, reducing proinflammatory mediators and demonstrating increased abdominal bacterial translocation during stress.⁸⁸

Inotropes

While EGDT incorporated dobutamine therapy to increase CO when ScvO2 remained low despite optimization of other parameters, as noted previously, subsequent trials did not indicate a benefit from EGDT compared to usual care.^21–24 However, septic cardiomyopathy is common, and personalized therapy may involve inotropic support with dobutamine for such patients.⁸⁹ Epinephrine — which has increased β₁ agonism and therefore increases inotropy more relative to norepinephrine — produced similar outcomes compared to the combination of norepinephrine and dobutamine and may be considered for addition or potentially as a first-line vasopressor for patients with septic cardiomyopathy or mixed shock.⁹⁰ Of note, levosimendan is contraindicated in septic shock, increasing arrhythmias without improving organ failure or mortality.⁹¹

Vasopressin

Septic shock patients may be vasopressin deficient,⁹² prompting interest in prioritizing this pure peripheral vasoconstrictor among patients needing a second-line vasopressor. Though individual trials have not shown definitive benefit, meta-analyses do support lower mortality with adjunctive vasopressin.¹¹ Importantly, while addition of low-dose vasopressin did not change mortality overall in the VASST trial, a sub-group analysis suggested improved outcomes among patients who started vasopressin with a norepinephrine dose < 15 mcg/min.⁹³ This finding is supported by a recent study in which an artificial intelligence agent “learned” that an optimal treatment strategy involved earlier vasopressin initiation.⁹⁴ Ongoing trials should provide high-quality data for the optimal dose of norepinephrine at which to trigger vasopressin initiation.^95,96

Other vasoactive agents

While initially counterintuitive, some studies have suggested vasodilator therapy (e.g., nitroglycerin) could help restore microcirculatory function in septic shock.⁹⁷ However, neither individual trials nor meta-analysis combining vasodilator agents with diverse mechanisms have shown benefit.⁹⁸ Similarly, though short-acting beta blockers were postulated to mitigate adverse effects of adrenergic overstimulation, potential benefit seen in earlier single-center trials was not borne out in recent multicenter trials.⁹⁹

Methylene blue and high-dose hydroxocobalamin may counter vasoplegia by scavenging of mediators of vasoplegia such as nitric oxide or inhibiting their production or effector pathways.^100,101 While their off-label use in septic shock appears to be increasing,¹⁰² the agents’ routine use in clinical care should await adequately powered trials measuring clinical outcomes rather than blood pressure response, especially since therapies inhibiting the nitric oxide pathway caused harm in past trials.^103,104

Vasopressor-associated ischemia

The association between high-dose vasoactive medications and end-organ ischemia or microcirculatory dysfunction and digital necrosis is likely overemphasized and is certainly confounded by patients’ underlying shock physiology. Among patients receiving norepinephrine at >1mcg/kg/min for ≥1 hour, 5.7% of patients had extremity ischemia and 2.8% were diagnosed with mesenteric ischemia. Most individual trials and meta-analyses have not suggested an excess risk of bowel or digital ischemia with the low doses of vasopressin used in current sepsis practice,^15,93,105 though evolving trends toward more conservative fluids will require continuing reassessment of this risk.

Central vs peripheral vasopressor administration

Historically, vasoactive medications were administered via a central venous catheter (CVC) due to the case report-based fear skin necrosis due to extravasation.^106,107 In contrast to the established complications of CVCs, however, the rate of serious extravasation complications is quite low. For instance, there were only 3 extravasation events among 500 patients who received peripheral vasopressors in the CLOVERS trial, of whom none required intervention.^{108,109,110,59} Guidelines now recommend not delaying vasopressor initiation for CVC placement.⁵ However, institutional and clinician practice varies regarding dose- and time-based thresholds for CVC placement, and optimal thresholds are unclear.^11,111,112

Conclusions

Evidence to guide the hemodynamic management of septic shock continues to evolve, but bedside clinicians still confront large gaps regarding optimal blood pressure, fluid resuscitation and deresuscitation, management of hemodynamic incoherence, and the timing of initiation of first- and second-line vasopressors. In addition to validated therapies targeting microcirculatory dysfunction, trials evaluating therapeutic targets and treatments specific to septic shock phenotypes are needed.

Clinics care points.

• Initial IV fluid resuscitation with 30 ml/kg of balanced crystalloids for septic shock remains reasonable.

• Dynamic fluid responsiveness assessments are likely valuable in septic shock, though evidence supporting their impact on patient-centered outcomes is limited.

• Clinicians employing lactate to guide hemodynamic resuscitation must consider whether abnormal clearance truly reflects inadequate tissue perfusion.

• Norepinephrine is the first-line vasopressor for septic shock and may be safely administered via peripheral IV given appropriate site selection and monitoring.

KEY POINTS.

• While lactate clearance can be a valuable septic shock resuscitation target, the potential for persistently elevated lactate not due to inadequate tissue perfusion complicates bedside application.

• Balanced crystalloids are the preferred resuscitation fluid in septic shock.

• Dynamic assessment strategies are likely valuable tools to guide fluid resuscitation in septic shock, though evidence supporting their impact on mortality and other patient-centered outcomes are lacking.

• Norepinephrine is the first-line vasopressor for septic shock and may be safely administered via peripheral IV given appropriate site selection and monitoring.