Therapeutic Therapeutic strategies for acute strategies for acute

lung injurylung injuryCME review article in CME review article in

Critical care medicine 2010 Critical care medicine 2010 Vol.38,No.8Vol.38,No.8

Dr Wahid AltafDr Wahid Altaf

StudyStudy

Goal : Provide practical evidence-Goal : Provide practical evidence-based review to assist care for patients based review to assist care for patients with severe acute lung injury and with severe acute lung injury and acute respiratory distress syndrome.acute respiratory distress syndrome.

Data resource: Pubmed.Data resource: Pubmed. Study selection: ALI/ARDS.Study selection: ALI/ARDS. Data synthesis :Author review.Data synthesis :Author review. Conclusion: Definition, therapies and Conclusion: Definition, therapies and

guidelines for ARDS. guidelines for ARDS.

Severe ARDS definitionSevere ARDS definition

Canada and Australia :One of the following Canada and Australia :One of the following criteria while receiving lung-protective criteria while receiving lung-protective ventilation strategyventilation strategy

Refractory hypoxemiaRefractory hypoxemia Refractory acidosisRefractory acidosis Refractory barotraumasRefractory barotraumas United Kingdom and Ireland: One of the United Kingdom and Ireland: One of the

followingfollowing Lung injury score > 3Lung injury score > 3 Uncompensated hypercapnia. Uncompensated hypercapnia.

Initial evaluationInitial evaluation

Evaluate underlying cause.Evaluate underlying cause.

Treat underlying cause.Treat underlying cause.

Alternate diagnosis if cause not Alternate diagnosis if cause not found.found.

Therapeutic StrategiesTherapeutic Strategies

Initial InterventionsInitial Interventions

Low Tidal volumeLow Tidal volume

Low inspiratory pressuresLow inspiratory pressures

Moderate PEEPModerate PEEP

Fluid conservative hemodynamicFluid conservative hemodynamic

management if possible.management if possible.

Strategies for improving Strategies for improving life- threatening hypoxemia.life- threatening hypoxemia.

Recruitment Manoeuvres and High PEEP.Recruitment Manoeuvres and High PEEP. Rationale: Aerate collapsed and flooded Rationale: Aerate collapsed and flooded alveoli to improve oxygenation, reduce alveoli to improve oxygenation, reduce VILI and improve compliance.VILI and improve compliance. Risks: Over inflation of non collapsed Risks: Over inflation of non collapsed alveoli, decreased alveolar fluid alveoli, decreased alveolar fluid clearance, additional VALI, clearance, additional VALI, hemodynamic compromise( decreased hemodynamic compromise( decreased

Blood Blood pressure and arrhythmias).pressure and arrhythmias).

Evidence for Recruitment Evidence for Recruitment Manoeuvres and High PEEPManoeuvres and High PEEP

Three large multicentre trials found no Three large multicentre trials found no significant difference in mortality rates.significant difference in mortality rates.

Recent trials reveal significant benefits in Recent trials reveal significant benefits in multiple secondary outcomesmultiple secondary outcomes

Canada and Australia study. Fewer Canada and Australia study. Fewer episodes of refractory hypoxemia and episodes of refractory hypoxemia and deaths related to it.deaths related to it. France Study( EXPRESS). More ventilator France Study( EXPRESS). More ventilator

free days, more organ failure free days and free days, more organ failure free days and reduced use of rescue therapies for severe reduced use of rescue therapies for severe hypoxemia.hypoxemia.

RecommendationsRecommendations

Consider earlier application for refractory Consider earlier application for refractory hypoxemia when PP< 30 cm of water and hypoxemia when PP< 30 cm of water and after achieving patient ventilator after achieving patient ventilator synchrony.synchrony.

Avoid RM in patients with Shock, Avoid RM in patients with Shock, pneumothorax or with focal disease.pneumothorax or with focal disease.

Assess improvement in oxygenation and Assess improvement in oxygenation and compliance at regular intervals.compliance at regular intervals.

Avoid/Abort if no improvement, worsened Avoid/Abort if no improvement, worsened hypotension or hypoxemia.hypotension or hypoxemia.

Prone positioningProne positioning

Rationale: Recruitment of dependent Rationale: Recruitment of dependent atelectatic lung to improve V/Q atelectatic lung to improve V/Q mismatching.mismatching.

Risks: Local complications and those due Risks: Local complications and those due to turning patients.to turning patients.

Evidence: No survival benefits in Four Evidence: No survival benefits in Four RCT’s but two trials noted improvement in RCT’s but two trials noted improvement in survival, oxygenation and plateau survival, oxygenation and plateau pressures after keeping patients prone for pressures after keeping patients prone for 20 hrs daily.20 hrs daily.

RecommendationsRecommendations

Consider for patients with severe Consider for patients with severe ARDS and life threatening hypoxemia ARDS and life threatening hypoxemia and/or elevated plateau pressures.and/or elevated plateau pressures.

Guidelines to prevent complications.Guidelines to prevent complications. Target prone positioning for at least Target prone positioning for at least

20 hrs daily.20 hrs daily. If no improvement in oxygenation by If no improvement in oxygenation by

end of day don’t continue and end of day don’t continue and consider another therapy.consider another therapy.

High-frequency oscillatory High-frequency oscillatory ventilationventilation

Rationale: Uses low tidal volumes and Rationale: Uses low tidal volumes and high mean airway pressure to achieve high mean airway pressure to achieve lung recruitment and improve lung recruitment and improve oxygenation.oxygenation.

Risks: Hemodynamic deterioration, Risks: Hemodynamic deterioration, barotraumas ,Ventilator asynchrony.barotraumas ,Ventilator asynchrony.

Evidence: Several studies reveal Evidence: Several studies reveal improved oxygenation after early improved oxygenation after early administration.administration.

RecommendationRecommendation

Institute HFOV earlier in severe ARDS Institute HFOV earlier in severe ARDS patients.patients.

Not to be used in patients with Not to be used in patients with shock, Severe airway obstruction, shock, Severe airway obstruction, Intracranial haemorrhage or Intracranial haemorrhage or refractory barotraumas and use refractory barotraumas and use cautiously in severely acidotic cautiously in severely acidotic patients.patients.

Inhaled Nitric Oxide.Inhaled Nitric Oxide.

Rationale: Redistributes blood flow Rationale: Redistributes blood flow towards well ventilated lungs towards well ventilated lungs improving oxygenation, attenuates improving oxygenation, attenuates inflammatory response. May be inflammatory response. May be cytotoxic to epithelial cells as well.cytotoxic to epithelial cells as well.

Evidence and Risks: No survival Evidence and Risks: No survival benefits in fact trend towards benefits in fact trend towards increased mortality rates and renal increased mortality rates and renal dysfunction.dysfunction.

RecommendationRecommendation

Consider in life threatening hypoxemia Consider in life threatening hypoxemia if previous interventions fail.if previous interventions fail.

Initiate at 1 ppm and increase every Initiate at 1 ppm and increase every 30 mins until improved oxygenation is 30 mins until improved oxygenation is achieved but don’t exceed 10 ppm, if achieved but don’t exceed 10 ppm, if no improvement gradually no improvement gradually discontinue, if improvement decrease discontinue, if improvement decrease dose daily to minimum required to dose daily to minimum required to achieve oxygenation but don’t use for achieve oxygenation but don’t use for more than 4 days.more than 4 days.

GlucocorticoidsGlucocorticoids

Rationale and risks: Helps by inhibiting Rationale and risks: Helps by inhibiting neutrophil activation, fibroblast proliferation, neutrophil activation, fibroblast proliferation, and collagen deposition. May increase and collagen deposition. May increase incidence of severe neuromyopathic events. incidence of severe neuromyopathic events. Subjects started on steroids 14 days after Subjects started on steroids 14 days after diagnosis had increased mortality rates.diagnosis had increased mortality rates.

Evidence: Clinical trials show no survival Evidence: Clinical trials show no survival benefits, two small RCT’s show improvement benefits, two small RCT’s show improvement in oxygenation and lung injury scores for up in oxygenation and lung injury scores for up to 1 week.to 1 week.

RecommendationRecommendation Consider steroids when previous therapies Consider steroids when previous therapies

have failed.have failed. Not to initiate after 14 days of diagnosis Not to initiate after 14 days of diagnosis

and in patients on neuromuscular blockers.and in patients on neuromuscular blockers. Use methyl prednisolone at dose of Use methyl prednisolone at dose of 1 mg/kg/day assess in 3 days if no 1 mg/kg/day assess in 3 days if no

improvement discontinue, if improvement improvement discontinue, if improvement continue (optimal duration unknown, may continue (optimal duration unknown, may be 7 days), physician to weigh risks and be 7 days), physician to weigh risks and benefits and underlying infection to be benefits and underlying infection to be treated appropriately.treated appropriately.

Strategies for improving life Strategies for improving life threatening respiratory threatening respiratory

acidosisacidosis Buffer therapyBuffer therapyRationale: Severe respiratory acidosis Rationale: Severe respiratory acidosis

may deter some physicians from may deter some physicians from employing lung protective strategies.employing lung protective strategies.

Evidence and risks: Sodium bicarbonate Evidence and risks: Sodium bicarbonate (increases partial pressure of co2) or (increases partial pressure of co2) or tris-hydroxymethyl aminomethane tris-hydroxymethyl aminomethane infusion (s/e volume overload, infusion (s/e volume overload, hyperkalemia and hypoglycaemia).hyperkalemia and hypoglycaemia).

RecommendationsRecommendations

For life threatening respiratory For life threatening respiratory acidosis consider tris-hydroxy methyl acidosis consider tris-hydroxy methyl aminomethane (THMA) provided aminomethane (THMA) provided there is no renal dysfunction. there is no renal dysfunction. Glucose and potassium levels to be Glucose and potassium levels to be monitored. If THMA contraindicated monitored. If THMA contraindicated then use bicarbonate infusion then use bicarbonate infusion cautiously.cautiously.

Consider renal replacement therapy.Consider renal replacement therapy.

Strategy for refractory Strategy for refractory casescases ECLSECLS

Rationale: performs gas exchange Rationale: performs gas exchange artificially and gives rest to lungs. ECMO or artificially and gives rest to lungs. ECMO or EC CO2 removal circuits.EC CO2 removal circuits.

Risks: Associated with anticoagulation and Risks: Associated with anticoagulation and large vascular access.large vascular access.

Evidence: Earlier studies dismal outcomes, Evidence: Earlier studies dismal outcomes, recent trial about transferring patients to recent trial about transferring patients to tertiary centre for management for severe tertiary centre for management for severe ARDS showed improved outcome.ARDS showed improved outcome.

RecommendationsRecommendations

Consider when previous therapies Consider when previous therapies fail.fail.

ECMO or EC Co2 removal should be ECMO or EC Co2 removal should be used as part of protocol at used as part of protocol at experienced medical centres.experienced medical centres.

Thanks.Thanks.