Acute Respiratory Distress Syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) is an acute, diffuse inflammatory lung injury that increases pulmonary vascular permeability, causes widespread loss of aerated lung tissue, and produces hypoxemia refractory to simple oxygen therapy. It is not a single disease but a common final pathway triggered by a wide range of pulmonary and extrapulmonary insults — most often sepsis, pneumonia, aspiration, major trauma, or pancreatitis.^[1] ARDS is diagnosed and graded using the Berlin Definition: acute onset within 1 week of a known insult, bilateral opacities not fully explained by effusion, collapse, or nodules, respiratory failure not fully explained by cardiac failure or fluid overload, and a PaO₂/FiO₂ ratio that stratifies severity into mild, moderate, and severe.^[1]

The single most important concept for a pharmacist to hold onto is that ARDS management is primarily supportive, not primarily a drug-therapy disease — lung-protective mechanical ventilation is the cornerstone of care, and no drug has ever been shown to independently reduce ARDS mortality the way it has in sepsis or an acute coronary syndrome.^[2] That does not mean pharmacotherapy is unimportant: real, specific, high-stakes pharmacist contributions exist throughout this chapter — correct neuromuscular blockade dosing and monitoring, weighing the genuinely evolving corticosteroid evidence, executing a conservative fluid strategy safely with diuretics, and getting sedation/analgesia strategy right for a ventilated patient — but every one of these sits around the ventilator strategy, not in place of it.

Presentation

ARDS presents as acute, progressive dyspnea and tachypnea with hypoxemia that does not correct with modest increases in supplemental oxygen, typically emerging over hours to days (and by definition within 1 week) after a known clinical insult or a new/worsening respiratory symptom.^[1] Auscultation often reveals diffuse crackles rather than focal findings, and the patient frequently appears more distressed than a simple pneumonia or exacerbation would explain. Because ARDS is a syndrome triggered by an underlying insult, the presenting picture is often dominated by that trigger (fever and productive cough in pneumonia-triggered ARDS, hypotension and altered mentation in sepsis-triggered ARDS, epigastric pain in pancreatitis-triggered ARDS) with progressive hypoxemic respiratory failure developing on top of it — recognizing that overlap is often what catches ARDS early rather than after intubation has already become unavoidable.

• Sepsis — the single most common precipitant of ARDS.
• Pneumonia, bacterial or viral (including influenza, COVID-19, and other respiratory viruses).
• Aspiration of gastric contents.
• Severe trauma, particularly with shock, pulmonary contusion, or multiple blood product transfusions.
• Acute pancreatitis.
• Massive or rapid blood product transfusion (transfusion-related acute lung injury, TRALI).
• Inhalational injury, smoke exposure, or near-drowning.
• Drug overdose.
• Older age, chronic alcohol use, hypoalbuminemia, and higher baseline severity-of-illness scores are all associated with a higher risk of developing ARDS after a given insult, and with worse outcomes once it develops.
• A prior episode of ARDS does not confer meaningful protection against a future episode.

The Berlin Definition

ARDS is diagnosed using 4 criteria, all of which must be met.^[1]

Severity grading — PaO₂/FiO₂ ratio

Severity is assessed with the patient on PEEP or CPAP of at least 5 cm H₂O — mild ARDS may be supported with non-invasive ventilation or CPAP if the setting allows it safely, but moderate and severe ARDS almost always require invasive mechanical ventilation.^[1]

A live calculator is intentionally not provided for the PaO₂/FiO₂ ratio here — it is a single division that the bedside blood gas and ventilator display already provide, and the teaching table above is what actually needs to be understood (the exclusion-of-cardiac-cause and imaging criteria, not just the ratio) to apply the definition correctly.

Investigations

• Arterial blood gas for PaO₂/FiO₂ — obtain and trend serially, not as a single snapshot, since severity can shift quickly in either direction.
• Chest radiograph or CT to confirm bilateral opacities and help exclude an alternative explanation (large effusion, lobar collapse).
• Echocardiography when the cause of pulmonary edema is not clearly explained by an identified ARDS risk factor, to help exclude a primarily cardiogenic process; natriuretic peptides (BNP/NT-proBNP) may support this assessment but are not diagnostic alone and can be elevated in critical illness for other reasons.
• Source-directed workup based on the suspected trigger: blood/sputum/respiratory cultures and a full sepsis workup (see the Sepsis chapter) for a suspected infectious trigger, lipase/amylase and abdominal imaging for suspected pancreatitis, and a careful transfusion history and timeline when TRALI is possible.

• Recognize ARDS early using the Berlin Definition and grade severity accurately, since severity drives the escalation ladder.
• Deliver lung-protective ventilation to every patient with ARDS — low tidal volume, limited plateau pressure, and an appropriate PEEP strategy for severity.
• Maintain adequate oxygenation (generally SpO2 88-95% or PaO2 55-80 mmHg) while explicitly accepting permissive hypoxemia and hypercapnia trade-offs rather than escalating ventilator settings to normalize numbers at the cost of lung injury.
• Identify and treat the underlying trigger directly — source control and antimicrobial therapy for an infectious cause, management of pancreatitis, evaluation of a transfusion reaction.
• Use prone positioning for moderate-severe disease, and escalate to ECMO referral early when hypoxemia remains refractory, rather than as a last resort.
• Apply a conservative fluid strategy once shock has resolved and the patient is hemodynamically stable.
• Use targeted, situational pharmacotherapy — neuromuscular blockade, corticosteroids — only where a specific indication applies, not routinely for every patient with ARDS.
• Minimize iatrogenic harm: avoid unnecessarily deep or prolonged sedation, avoid unnecessarily prolonged paralysis, and prevent ventilator-associated pneumonia, ICU-acquired weakness, and delirium.
• Support the earliest safe liberation from mechanical ventilation and address post-intensive-care recovery needs.

Lung-protective ventilation — the true cornerstone of ARDS care

• Tidal volume around 6 mL/kg predicted body weight (PBW, calculated from height and sex — never actual body weight), acceptable range 4-8 mL/kg PBW.^[2]
• Plateau pressure below 30 cm H₂O, minimizing driving pressure (plateau pressure minus PEEP) where achievable.^[2]
• Accept permissive hypercapnia and a lower target SpO₂/PaO₂ (generally SpO₂ 88-95% or PaO₂ 55-80 mmHg) rather than using injurious ventilator settings to normalize gas exchange; avoid hyperoxia as well as hypoxemia.
• Use a higher-PEEP strategy from a standard PEEP/FiO₂ table for moderate-severe ARDS; avoid an aggressive incremental recruitment-maneuver-based PEEP titration strategy, which has been associated with harm in trial evidence.^[2]
• Do not use high-frequency oscillatory ventilation (HFOV) routinely — trial evidence in moderate-severe ARDS has shown no benefit and a signal of harm; it is not a routine rescue strategy.^[2]

Prone positioning

For moderate-severe ARDS with PaO₂/FiO₂ under roughly 150 despite optimized ventilator settings, prone positioning for sessions of at least 16 consecutive hours reduces mortality — this is one of the few ARDS interventions with genuine mortality-benefit evidence, and should be started early (after a brief period of stabilization) rather than reserved as a late rescue measure.^[3] Prone positioning requires a trained team and careful protocol for safe turning, pressure-injury prevention, and line/tube security — see the Pressure Injuries chapter for skin-protection principles that apply directly here.

Conservative fluid management

Once shock has resolved and the patient is hemodynamically stable, target an even-to-negative fluid balance using a protocolized diuresis strategy (see Pharmacologic Treatment Options) rather than continued liberal fluid administration — this shortens the duration of mechanical ventilation and ICU stay without increasing non-pulmonary organ failure, though it has not been shown to independently reduce mortality.^[6] Sequencing matters: this applies only after initial shock resuscitation is complete — a patient with concurrent septic or hypovolemic shock still needs the fluid resuscitation described in the Sepsis chapter first; the conservative strategy is a subsequent phase of care, not a substitute for adequate initial resuscitation.

Treat the underlying trigger

Ventilator management alone will not resolve ARDS if the precipitating insult is left untreated — source-directed antimicrobial therapy for a pneumonia or sepsis trigger (see the Sepsis and Community-Acquired Pneumonia chapters), management of pancreatitis, and evaluation of a suspected transfusion reaction are all core, concurrent parts of ARDS care, not an afterthought once the ventilator is set up.

Extracorporeal membrane oxygenation (ECMO)

Veno-venous ECMO is a rescue option for refractory severe hypoxemia despite optimized lung-protective ventilation and prone positioning, provided at expert centres with the necessary experience and infrastructure. Refer early once hypoxemia is proving refractory to standard measures rather than waiting until multi-organ failure has developed — outcomes are meaningfully worse with delayed referral.

Standard critical-care supportive bundle

• Analgesia-first, lightest-effective sedation strategy with daily interruption/targeting once appropriate (see Pharmacologic Treatment Options).
• Daily assessment for spontaneous awakening and spontaneous breathing trial candidacy, to support the earliest safe liberation from mechanical ventilation.
• Pharmacologic VTE prophylaxis unless contraindicated.
• Stress ulcer prophylaxis in patients at elevated GI bleeding risk.
• Early enteral nutrition once hemodynamically stabilized.
• A restrictive red blood cell transfusion strategy rather than a liberal one.
• Early mobilization once feasible, to reduce ICU-acquired weakness — a particular concern in any patient who has received neuromuscular blockade or prolonged deep sedation.

Pregnancy

Breastfeeding

This is rarely an immediate clinical question during acute critical illness, since a patient with moderate-severe ARDS is typically sedated and mechanically ventilated. Once the patient has recovered enough for the question to be relevant, dexamethasone and methylprednisolone at standard treatment doses are both considered compatible with breastfeeding; confirm specifics against each drug's own Drug Database entry.

Renal impairment

Cisatracurium undergoes organ-independent Hofmann elimination (spontaneous degradation at physiologic pH and temperature) rather than renal or hepatic clearance — a genuine practical advantage that makes it a reasonable neuromuscular blocking agent choice in renal impairment with minimal dose adjustment needed. Furosemide may need higher doses in renal impairment or diuretic resistance; when executing a conservative fluid strategy in a patient with concurrent or evolving acute kidney injury, balance fluid removal against renal perfusion carefully and involve nephrology rather than pursuing an increasingly negative balance in isolation.

Hepatic impairment

Cisatracurium's Hofmann elimination is also independent of hepatic function, making it a preferred neuromuscular blocking agent in hepatic impairment. Sedative and analgesic dosing (propofol, fentanyl) may need downward adjustment with significant hepatic impairment given their hepatic metabolism — review each agent's product monograph for specifics.

Obesity

Calculate tidal volume using predicted body weight (from height and sex) — never actual body weight; using actual body weight in an obese patient produces a clinically significant tidal volume overshoot and is one of the most common, most consequential dosing errors in ARDS care. Sedative, analgesic, and neuromuscular blocking agent dosing, by contrast, is generally based on actual or adjusted body weight per the individual agent's own dosing guidance — the distinction between PBW-based ventilator dosing and weight-based drug dosing is worth stating explicitly, since conflating the two in either direction is a real error.

Older adults

Increased susceptibility to sedative accumulation and delirium argues for an even more deliberately light sedation target and vigilant delirium screening. Older adults also carry a higher baseline risk of ICU-acquired weakness, which strengthens the case for reserving neuromuscular blockade strictly for a specific indication rather than routine use, and for early mobilization once feasible.

COVID-19 and other viral triggers

General ARDS lung-protective ventilation, PEEP, and prone-positioning principles apply the same way regardless of trigger. Virus-specific antiviral and immunomodulatory therapy (including the specific dexamethasone evidence base that emerged from COVID-19 respiratory failure trials) is addressed in the COVID-19 and Influenza chapters rather than duplicated here — treat this chapter's corticosteroid guidance as the general ARDS evidence base, and defer to the virus-specific chapter for a viral trigger.

Trend PaO₂/FiO₂ serially (not as a single value) to track severity and guide escalation or de-escalation, and review plateau pressure and driving pressure at every ventilator check to confirm lung-protective targets are actually being met, not merely intended.^[2] Screen for delirium and assess sedation depth against a validated scale daily, and assess spontaneous awakening/breathing trial candidacy daily once the patient is stabilizing, to support the earliest safe liberation from mechanical ventilation.

Neuromuscular blockade

Use train-of-four monitoring where the infusion continues beyond the initial period, and reassess the ongoing need for it daily — discontinue at 48 hours per the trial-based protocol unless a specific ongoing indication genuinely persists.^[4] Because a paralyzed patient cannot report distress, concurrent sedation and analgesia adequacy must be actively confirmed through physiologic surrogates (heart rate, blood pressure, processed EEG monitoring where available) rather than assumed — under-sedation during paralysis is a serious safety failure, not a comfort issue.

Corticosteroids

Monitor blood glucose closely, watch for secondary infection, and reassess the ongoing need daily rather than allowing an open-ended course — follow the specific completed regimen (see Drug Tables) rather than continuing indefinitely by default.^[5]

Conservative fluid strategy

Review daily fluid balance, renal function, and electrolytes alongside diuresis, and track perfusion markers (lactate, urine output, mentation) to confirm the conservative strategy is not producing under-resuscitation or organ hypoperfusion rather than its intended benefit.^[6]

Transitions of care

Medication reconciliation at every transition — ICU to ward, and hospital to home — is essential: sedatives, neuromuscular blocking agents, and corticosteroids started acutely must be actively and deliberately stopped as the patient recovers, not silently carried forward through a handoff. Before discharge, screen for physical, cognitive, and psychological impairment consistent with post-intensive care syndrome, and arrange follow-up for anything identified — mechanically ventilated ARDS survivors are at meaningfully elevated risk for this.

1. Worsening hypoxemia despite lung-protective ventilation at the intended PEEP: confirm plateau and driving pressures are actually within target (not merely intended), escalate PEEP per the standard table, and begin prone positioning if not already started and PaO₂/FiO₂ is under roughly 150.^[2]
2. Persistent patient-ventilator dyssynchrony despite optimized analgesia and sedation: consider a time-limited neuromuscular blockade infusion rather than continuing to escalate sedation depth indefinitely.
3. Refractory severe hypoxemia despite lung-protective ventilation, adequate PEEP, and prone positioning: refer early to an ECMO-capable centre — this should happen as hypoxemia proves refractory, not once multi-organ failure has already set in.
4. No improvement, or worsening, despite standard supportive measures: reassess for an alternative or missed diagnosis (cardiogenic pulmonary edema, pulmonary embolism, diffuse alveolar hemorrhage, acute eosinophilic pneumonia) rather than assuming this is simply refractory ARDS.
5. New fever or clinical deterioration during the ICU course: reassess for an uncontrolled or new infectious source — ventilator-associated pneumonia, a missed original source, or drug fever — rather than attributing it to the natural course of ARDS.
6. Persistent oliguria or apparent fluid intolerance during a conservative fluid strategy: reassess volume status and renal function before continuing aggressive diuresis, and involve nephrology if acute kidney injury is progressing.

• Calculating tidal volume from actual body weight instead of predicted body weight — a common, clinically significant dosing error, especially in obese patients.
• Treating ARDS as primarily a pharmacotherapy problem — reaching for a drug (a corticosteroid, neuromuscular blockade) before lung-protective ventilation and, where indicated, prone positioning are actually optimized.^[2]
• Continuing an aggressive fluid-resuscitation strategy well past the point of hemodynamic stability instead of transitioning to a conservative fluid strategy once shock has resolved.^[6]
• Starting corticosteroids very late in the illness course (beyond roughly 2 weeks from ARDS onset) — evidence from the persistent-ARDS steroid literature suggests possible harm rather than benefit at that point, not simply reduced benefit.
• Initiating neuromuscular blockade without first ensuring adequate concurrent sedation and analgesia — a paralyzed, under-sedated patient is a serious safety failure.
• Continuing neuromuscular blockade indefinitely rather than reassessing daily and stopping at 48 hours (or sooner) absent a specific ongoing indication.^[4]
• Applying an aggressive incremental PEEP-titration or recruitment-maneuver strategy instead of a standard PEEP/FiO₂ table — trial evidence favours the table-based approach.^[2]
• Delaying prone positioning or ECMO referral until the patient is already in multi-organ failure, rather than initiating them at the point the evidence supports.^[3]
• Focusing solely on ventilator management while missing or delaying treatment of the underlying trigger (infection, pancreatitis, a transfusion reaction).
• Letting acutely started sedatives, neuromuscular blocking agents, or corticosteroids continue by default through care transitions instead of actively stopping them as the patient improves.

How to use this table: Doses are adult ICU doses and require patient-specific confirmation, including renal/hepatic adjustment where relevant. Select any drug name to open its complete Pharmasist Drug Database page. Antimicrobial therapy for an infectious ARDS trigger is intentionally not repeated here — see the Sepsis and Community-Acquired Pneumonia drug tables for that content.

Neuromuscular Blocking Agent

Reserve for a specific indication (persistent patient-ventilator dyssynchrony, refractory hypoxemia, or persistently elevated plateau/driving pressure despite optimized sedation) — not routine for every severe ARDS patient. Never administer without confirmed, adequate concurrent sedation and analgesia.

Corticosteroids

A genuinely evolving evidence area. The 2024 SCCM focused update conditionally suggests corticosteroids for critically ill adults with ARDS (moderate-certainty mortality benefit) but does not endorse a specific molecule, dose, or duration. Avoid initiating beyond roughly 2 weeks after ARDS onset — the persistent-ARDS steroid literature suggests possible harm, not simply reduced benefit, with late initiation.

Analgesia and Sedation

Use an analgesia-first strategy — treat pain before adding or escalating a sedative — and target the lightest sedation level that meets the clinical goal, deepening only when specifically required for ventilator synchrony, prone positioning, or concurrent neuromuscular blockade.

Diuretic (Conservative Fluid Management)

Apply only once shock has resolved and the patient is hemodynamically stable — never during the active fluid-resuscitation phase of septic or hypovolemic shock.