Acute Hypoxemic Acute Hypoxemic Respiratory FailureRespiratory Failure

Margaret J. Neff, MD MScMargaret J. Neff, MD MSc

Assistant Professor of Medicine Assistant Professor of Medicine Pulmonary & Critical CarePulmonary & Critical Care

““Your patient’s sat is 88%”Your patient’s sat is 88%”

• 55 y/o man with a history of mild COPD55 y/o man with a history of mild COPD

• 3 days s/p elective surgery3 days s/p elective surgery• bilateral knee replacementsbilateral knee replacements

• Uneventful post-operative course except Uneventful post-operative course except for an ileus and ongoing complaints of for an ileus and ongoing complaints of painpain

• Had been on room air during the dayHad been on room air during the day• You’re called with this sat at 3 a.m.You’re called with this sat at 3 a.m.

““He says he can’t catch his breath”He says he can’t catch his breath”

• Repeat sat confirmed: 88%Repeat sat confirmed: 88%

• CXR done in the a.m. had shown mild CXR done in the a.m. had shown mild bibasilar atelectasisbibasilar atelectasis• possible RLL infiltratepossible RLL infiltrate

• ABG: 7.45/32/60 on room airABG: 7.45/32/60 on room air

• On high flow oxygen, his PaOOn high flow oxygen, his PaO2 2 is 100is 100

Causes of HypoxemiaCauses of Hypoxemia

• Decreased PiODecreased PiO22

• HypoventilationHypoventilation

• Diffusion abnormalityDiffusion abnormality

• Ventilation/Perfusion mismatchVentilation/Perfusion mismatch• Dead space (high V/Q)Dead space (high V/Q)• Shunt (low V/Q)Shunt (low V/Q)

Decreased PiODecreased PiO2 2

• High altitudeHigh altitude

• IatrogenicIatrogenic• i.e. wrong gas mixturei.e. wrong gas mixture

• Unlikely to be an issue in clinical Unlikely to be an issue in clinical hypoxemiahypoxemia

• Aa gradient normalAa gradient normal

HypoventilationHypoventilation• Essentially alveolar hypoventilationEssentially alveolar hypoventilation

• CNS drive depressedCNS drive depressed

• Pain and splintingPain and splinting

• Thoracic or abdominal restrictionThoracic or abdominal restriction

• Commonly seen clinicallyCommonly seen clinically• May be manifest as bibasilar atelectasisMay be manifest as bibasilar atelectasis• Hypoxemia reverses if take deep breathHypoxemia reverses if take deep breath

• Aa gradient normalAa gradient normal

Diffusion AbnormalityDiffusion Abnormality

• Acute or chronic disease which affects the Acute or chronic disease which affects the ability for oxygen to transport from ability for oxygen to transport from alveolus to capillaryalveolus to capillary

• Common in moderate to severe lung Common in moderate to severe lung disease, vascular disease, etcdisease, vascular disease, etc

• Unlikely to cause acute hypoxemiaUnlikely to cause acute hypoxemia

• Aa gradient increasedAa gradient increased

Ventilation/Perfusion MismatchVentilation/Perfusion MismatchDead SpaceDead Space

• Areas with normal ventilation, reduced Areas with normal ventilation, reduced perfusion (high V/Q ratio)perfusion (high V/Q ratio)

• Pulmonary embolus is a good examplePulmonary embolus is a good example• Dead space and poor CODead space and poor CO2 2 removal removal

require increased minute ventilationrequire increased minute ventilation• May or may not be hypoxemiaMay or may not be hypoxemia

• Aa gradient increasedAa gradient increased

Ventilation/Perfusion MismatchVentilation/Perfusion MismatchShuntShunt

• Areas with decreased ventilation and normal Areas with decreased ventilation and normal perfusion (low V/Q)perfusion (low V/Q)

• Consolidation from pneumoniaConsolidation from pneumonia• Can increase if lose ability for hypoxic Can increase if lose ability for hypoxic

pulmonary vasoconstrictionpulmonary vasoconstriction• non-selective vasodilators: nitrates, nipridenon-selective vasodilators: nitrates, nipride

• Poorly oxygen responsivePoorly oxygen responsive

• Aa gradient increasedAa gradient increased

““Your patient is still SOB”Your patient is still SOB”

• Unlikely a problem with PiOUnlikely a problem with PiO22 or diffusion or diffusion

• May be some degree of hypoventilation May be some degree of hypoventilation due to narcotic usedue to narcotic use

• Sputum with lots of polys and GPCSputum with lots of polys and GPC

• Repeat CXR shows consolidated RLLRepeat CXR shows consolidated RLL

• Other possibilities?Other possibilities?

““Your next admit is here”Your next admit is here”

• 45 y/o man with diabetes and urosepsis45 y/o man with diabetes and urosepsis• progressively hypotensive, tachypneicprogressively hypotensive, tachypneic

• Intubated for respiratory distress and Intubated for respiratory distress and hypoxemia: oxygen sat on high flow hypoxemia: oxygen sat on high flow oxygen of 90%oxygen of 90%

Effusion or Edema?Effusion or Edema?

“Bilateral infiltrates consistent with pulmonary edema”• meets radiographic criteria for

acute lung injury

CT reveals normal parenchyma but bilateral effusions

Courtesy of G. Rubenfeld

Pleural EffusionPleural Effusion

1 day later

After CT insertion

Acute Lung Injury (ALI)Acute Lung Injury (ALI)

• Clinical diagnosis (AECC definition)Clinical diagnosis (AECC definition)

• CXR: bilateral infiltrates consistent with CXR: bilateral infiltrates consistent with pulmonary edemapulmonary edema

• PaO2/FiO2 ratio PaO2/FiO2 ratio << 300 ( 300 (<< 200 for ARDS) 200 for ARDS)

• No evidence of left atrial hypertensionNo evidence of left atrial hypertension• PAWP PAWP << 18 if available 18 if available

AJRCCM 1994

ALI Risk FactorsALI Risk Factors• TraumaTrauma

• SepsisSepsis

• AspirationAspiration

• Multiple transfusionsMultiple transfusions

• Pancreatitis, overdose, near drowningPancreatitis, overdose, near drowning

• Still up to 20% of patients without a defined risk Still up to 20% of patients without a defined risk factorfactor• in other words, don’t have to have a risk to have in other words, don’t have to have a risk to have

ALI/ARDSALI/ARDS

ALI PathophysiologyALI Pathophysiology

• Inflammatory process and increased Inflammatory process and increased vascular permeabilityvascular permeability

• Bronchoalveolar lavage fluid: neutrophil Bronchoalveolar lavage fluid: neutrophil predominantpredominant• those with persistent neutrophils in BAL those with persistent neutrophils in BAL

tend to have a worse clinical coursetend to have a worse clinical course

ALI: clinical manifestationsALI: clinical manifestations

• Early in the course of ARDS, hypoxemia Early in the course of ARDS, hypoxemia often dominantoften dominant

• Due primarily to intrapulmonary Due primarily to intrapulmonary shuntingshunting• atelectasis and alveolar floodingatelectasis and alveolar flooding• disruption of normally protective hypoxic disruption of normally protective hypoxic

pulmonary vasoconstrictionpulmonary vasoconstriction

ALI: clinical manifestationsALI: clinical manifestations

• After 3-7 days, poor compliance can After 3-7 days, poor compliance can become the major problembecome the major problem• fibroproliferative stagefibroproliferative stage

• Increasing dead space (can exceed 70%)Increasing dead space (can exceed 70%)• fibrosis, microthrombi in vesselsfibrosis, microthrombi in vessels• can lead to pulmonary hypertension and can lead to pulmonary hypertension and

right heart dysfunctionright heart dysfunction

ALI: ManagementALI: Management

• Lung protective ventilationLung protective ventilation• 22% reduction in mortality 22% reduction in mortality • Tidal volume 6 ml/kg (PBW)Tidal volume 6 ml/kg (PBW)• Pst Pst << 30 cmH2O 30 cmH2O• allowing pH down to 7.15 if necessaryallowing pH down to 7.15 if necessary• confirms previous animal studies showing confirms previous animal studies showing

increased systemic inflammation with higher increased systemic inflammation with higher tidal volumes, precipitated by lung stretchtidal volumes, precipitated by lung stretch

NEJM 2000

Other Potential TherapiesOther Potential Therapies

• Prone positioning?Prone positioning?• Steroids?Steroids?• Anti-inflammatory agents?Anti-inflammatory agents?• Surfactant?Surfactant?• Anti-oxidants?Anti-oxidants?• Inhaled nitric oxide?Inhaled nitric oxide?

NONE PROVENNONE PROVEN

CorticosteroidsCorticosteroids

• Hypothesized to be effective due to Hypothesized to be effective due to intense inflammatory response seen in intense inflammatory response seen in ARDS patientsARDS patients• Bronchoalveolar lavage with >70% Bronchoalveolar lavage with >70%

neutrophils (normally < 2%)neutrophils (normally < 2%)• Plasma IL6 levels elevatedPlasma IL6 levels elevated

• Previous studies using steroids early in Previous studies using steroids early in ARDS have not proven beneficialARDS have not proven beneficial11

1 Crit Care Med 23:1294-1303

Steroids Late in ARDSSteroids Late in ARDS

• After first 3-7 days, ARDS progresses in After first 3-7 days, ARDS progresses in many patients to a fibrotic stagemany patients to a fibrotic stage• Proliferation of alveolar type II cellsProliferation of alveolar type II cells

• Several small studies of steroids at this Several small studies of steroids at this phasephase11

• Inconclusive, in part due to study designInconclusive, in part due to study design• Possibly due to the need for a balance of pro- Possibly due to the need for a balance of pro-

and anti-inflammatory mediatorsand anti-inflammatory mediators

1 JAMA 280:159-165

Recent Steroid TrialRecent Steroid Trial• NIH sponsored ARDS network (“LaSRS”)NIH sponsored ARDS network (“LaSRS”)

• 10 sites nationally conducting ARDS studies10 sites nationally conducting ARDS studies

• Enrolled patients at day 7-28 of ARDSEnrolled patients at day 7-28 of ARDS• Receive steroids 2mg/kg/d (tapered over 2 weeks)Receive steroids 2mg/kg/d (tapered over 2 weeks)

• 180 patients enrolled180 patients enrolled• No difference in mortality (increased with No difference in mortality (increased with

steroids if given >14 days after ALI)steroids if given >14 days after ALI)• Steroids: more vent-free days, shock-free days; Steroids: more vent-free days, shock-free days;

also more neuromuscular complicationsalso more neuromuscular complicationsNEJM 2006; 354(16):1671

FACTT StudyFACTT Study

• Liberal vs conservative fluid mgmtLiberal vs conservative fluid mgmt• No difference in mortalityNo difference in mortality• Conservative strategy resulted in better lung Conservative strategy resulted in better lung

fxn and shorter time on vent & in ICUfxn and shorter time on vent & in ICU• Fluid strategy initiated after shock resuscitationFluid strategy initiated after shock resuscitation

• PAC vs CVCPAC vs CVC• No difference in mortalityNo difference in mortality• More complications in PACMore complications in PAC

NEJM 2006; 354(21):2213-24 & NEJM 2006;354(24):2564-75

What else can we do What else can we do for ARDS patients?for ARDS patients?

• Minimize ICU-related complicationsMinimize ICU-related complications• HOB elevationHOB elevation• DVT prophylaxisDVT prophylaxis• Stress gastritis prophylaxisStress gastritis prophylaxis• Optimizing nutritionOptimizing nutrition

• Early enteral feeding +/- TPNEarly enteral feeding +/- TPN

• Invasive diagnostic strategies for ventilator-Invasive diagnostic strategies for ventilator-associated pneumoniaassociated pneumonia

• Tight glucose controlTight glucose control• Sedation managementSedation management

Pneumothorax

RCT of HOB ElevationRCT of HOB Elevation

• 1 year enrollment in MICU (Spain)1 year enrollment in MICU (Spain)• Randomized to HOB Randomized to HOB >> 45 45° or supine° or supine• Excluded if recent abd or neurosurgery, Excluded if recent abd or neurosurgery,

refractory shock, re-intubationrefractory shock, re-intubation• Endpoint: clinically or microbiologically Endpoint: clinically or microbiologically

confirmed pneumoniaconfirmed pneumonia• (not rigorously defined, though)(not rigorously defined, though)

• 86 patients enrolled86 patients enrolled• Mean age 65yr; 34% with COPDMean age 65yr; 34% with COPD

Lancet 1999;354:1851-8

ResultsResults

• Nosocomial pneumonia lower in semi-Nosocomial pneumonia lower in semi-recumbent grouprecumbent group• 8% vs 34% for clinically suspected8% vs 34% for clinically suspected• 5% vs 23% for micro proven5% vs 23% for micro proven

• Supine position and enteral feeding were Supine position and enteral feeding were independent risk factors for VAPindependent risk factors for VAP• Highest risk when both occurred togetherHighest risk when both occurred together

Ventilator Associated PneumoniaVentilator Associated Pneumonia

• Often difficult diagnosis to make Often difficult diagnosis to make clinicallyclinically• CXR in ALI patient is already abnormalCXR in ALI patient is already abnormal• ET aspirates may just reflect colonizationET aspirates may just reflect colonization• May be on antibiotics for surgical May be on antibiotics for surgical

procedures or other infectionsprocedures or other infections

VAP DiagnosisVAP Diagnosis

• RCT of 413 patients intubated for at least RCT of 413 patients intubated for at least 48 hours48 hours11

• Clinical suspicion of VAPClinical suspicion of VAP• No antibiotic change for prior 72 hoursNo antibiotic change for prior 72 hours

• Bronchoscopy vs ET aspirateBronchoscopy vs ET aspirate• Bronch: Reduced mortality at day 14, Bronch: Reduced mortality at day 14,

decreased antibiotic use, more antibiotic decreased antibiotic use, more antibiotic free days, more appropriate abx choicesfree days, more appropriate abx choices

1 Ann Intern Med 2000;132:621-30

Tight Glucose Control In ICUTight Glucose Control In ICU

• Recognized hyperglycemia/insulin resistance in Recognized hyperglycemia/insulin resistance in ICU patientsICU patients

• RCT of glucose control in SICU patientsRCT of glucose control in SICU patients• 2/3 cardiac surgery patients2/3 cardiac surgery patients• 13% with h/o diabetes13% with h/o diabetes

• Glucose goals: 80-110 vs 180-200Glucose goals: 80-110 vs 180-200• Decreased mortalityDecreased mortality

• (ICU) 4.6% vs 8%; (hospital) 10.9% vs 7.2%(ICU) 4.6% vs 8%; (hospital) 10.9% vs 7.2%

• Subsequent studies show benefit > 4yrs for CV Subsequent studies show benefit > 4yrs for CV surg patients; questions results in MICUsurg patients; questions results in MICU

N Engl J Med 2001;3451359-67; Eur Heart J 2006 Apr 11 Epub; NEJM 2006 354(5):449-61

Interruption of Sedative Interruption of Sedative Infusions in the ICUInfusions in the ICU

• Prospective, randomized trialProspective, randomized trial• 150 patients receiving continuous infusions150 patients receiving continuous infusions

• Targeted Ramsay 3-4Targeted Ramsay 3-4

• Randomized to daily interruption of infusion Randomized to daily interruption of infusion or standard careor standard care

• The intervention was disruption of infusion, The intervention was disruption of infusion, not controlling dosing or sedation targetsnot controlling dosing or sedation targets

• Once patient awake, investigator notified Once patient awake, investigator notified primary team and decision made regarding primary team and decision made regarding resuming infusion (not based on protocol)resuming infusion (not based on protocol)

Kress, et al. NEJM 2000; 342:1471-7

Better Outcomes with Interruption Better Outcomes with Interruption of Sedative (& Analgesic) Infusionof Sedative (& Analgesic) Infusion

• 2 fewer days on ventilator (5 days vs 7)2 fewer days on ventilator (5 days vs 7)

• 3.5 fewer days in the ICU (6.5 vs 10)3.5 fewer days in the ICU (6.5 vs 10)

• Fewer diagnostic tests to work up altered Fewer diagnostic tests to work up altered mental status (9% vs 27%)mental status (9% vs 27%)

• No difference in complicationsNo difference in complications• e.g. self-extubations (4% vs 7%)e.g. self-extubations (4% vs 7%)

Does Deep Sedation Predispose Does Deep Sedation Predispose to PTSD?to PTSD?

• Factual memory Factual memory protected againstprotected against post- post-traumatic stress disorder symptomstraumatic stress disorder symptoms

• Delusional memory was a risk for PTSDDelusional memory was a risk for PTSD• Implications:Implications:

• Deep sedation and complete amnesia may not be Deep sedation and complete amnesia may not be beneficial to patientsbeneficial to patients

• Side effects of drugs (hallucinations, nightmares) Side effects of drugs (hallucinations, nightmares) may be harmfulmay be harmful

Jones, et al. Crit Care Med 2001;29:573-80

ALI: OutcomesALI: Outcomes

• Improved mortality over the past 30 yearsImproved mortality over the past 30 years• 60% mortality reduced to 30-40%60% mortality reduced to 30-40%

• Most continue to improve lung function Most continue to improve lung function over the first yearover the first year• often left with abnormal diffusion capacityoften left with abnormal diffusion capacity

• Evidence to suggest some loss in Evidence to suggest some loss in neuropsychiatric function/testing and neuropsychiatric function/testing and neuromuscular functionneuromuscular function

Respiratory FailureRespiratory Failure

• Your 2 patients did wellYour 2 patients did well• Patient with pneumonia continued to Patient with pneumonia continued to

improve and transferred to rehab improve and transferred to rehab • Patient with urosepsis was in the ICU for 7 Patient with urosepsis was in the ICU for 7

days with ALI but was extubated and doing days with ALI but was extubated and doing well.well.

Acute Respiratory FailureAcute Respiratory Failure

• When faced with acute SOB, run through When faced with acute SOB, run through the list of possibilities while initiating the list of possibilities while initiating diagnostic testing and applying oxygendiagnostic testing and applying oxygen• Think of the clinical scenario to help you Think of the clinical scenario to help you

trim the possibilitiestrim the possibilities• See if interventions help See if interventions help • Diagnose and treat for the most life-Diagnose and treat for the most life-

threatening while you’re fine-tuning the threatening while you’re fine-tuning the diagnosisdiagnosis