CO2 Removal Is it an Important goal in Ventilation?

Yes (& No) Basic Considerations

CO2 REMOVAL IN VENTILATION Variable CO2: What’s the Problem?

• CO2 largest end product of (200ml/min) • Major determinant of pH

• CO2 levels very tightly controlled by central & peripheral CO2 & pH sensors – Can be blunted by drugs or disease

• CO2 regulation must evolutionarily be very important for such an intricate system to be naturally selected – pH control necessary for metabolic activity

– PaCO2 important in CNS & pulmonary auto-regulation of blood flow • For routine MV, target a mild hypocarbia to blunt respiratory drive Basic Considerations: CO2 & Ventilation

• Permissive : A strategy to limit adverse effects secondary to

• Contraindications to “permissive” high CO2 – Brain injury • ? Case Report of papilledema and raised ICP even with normal brain in extreme hypercapnia – Pregnancy (? Up to 60 mmHg) – Other conditions with extreme acidosis and hyerkalemia • Caution with targeted hypocapnea – Hyperventilation in Raised ICP /TBI • Temporarily decreases CBF  CBV  ICP • Worse functional neurological outcomes – Sub group analysis – At 3 & 6 but not at 12 months

Basic Considerations: CO2 & Ventilation

• Clinical Syndromes

– Chronic CO2 retention – Acute hypoventilatory failure – Severe ARDS • Dual/tricky situations CNS + RS injury – Poly trauma – Post CPR + aspiration – CVA & chest infection – ? Poisoning

Approach to high CO2 on Ventilator

• Target: CO2 or pH – Normal vs other?

• Ventilatory options to high CO2 – Increase RR &/or TV • Tracheostomy / Remove dead space

• O2 insufflation through ETT • Is hypercapnia or effects of MV worse – Baro-Trauma & Ventilator Associated Injury – Hemodynamic worsening-MAP/PEEPi CO2 in Spontaneous modes of Ventilation (NIV or tracheal tube) • Common error in intubated & ventilated patient – Patient on PSV – Low minute volume or apnoea alarm goes off – Doctor switches patient back to Control Mode – Unnecessary delays in weaning & extubation • Correct approach

– Check if patient comfortable & check PaCO2 • If awake and hypocapnic / normocapnic & alkalotic –  decrease PSV or wean and extubate

• If drowsy, high CO2 / acidosis Control mode and evaluate

Chronic CO2 Retention Syndromes

CO2 REMOVAL IN VENTILATION NIV (BiPAP) in Chronic Progressive Neuromuscular Disease • MND & muscular dystrophy

• Low SaO2 (air) + normal = Hypoventilation • Many symptoms attributed to hypoxia are due to hypoventilation & hypercarbia

• O2 will not relieve & may worsen these effects • NIV with room air will usually correct • NIV will relieve symptoms secondary to hypercarbia NIV in Progressive Neuromuscular Disease

• Main indications are clinical – Day time drowsiness & other CNS symptoms – Respiratory symptoms • Main aim is to give symptomatic relief • Some evidence of prolonging life • Focus must be on Quality of Life

NIV in Progressive Neuromuscular Disease

• Two main Strategies • “Elective” Nocturnal Ventilation – To relieve day time symptoms of drowsiness or impaired cognition • Day time Ventilation – To relieve respiratory symptoms – Not “elective” – Liberally as needed NIV in Chronic Non-Progressive Hypoventilation Syndromes • OSA & Obesity Hypoventilation syndrome – Similar considerations as in neuromuscular disease – “Elective” nocturnal NIV • Prevents nocturnal desaturation, hypercapnea & repeated arousal • Improves day time symptoms – ? Reversible risk factor for CAD & CCF • COPD – Usually need ventilation for acute exacerbation CO2 Target in Chronic Hypercarbic Diseases

• Best NOT to set a CO2 target – Avoid routine ABGs • Use Spontaneous mode of ventilation – PSV or BiPAP • Patient matches ventilatory pattern to need

• The Correct CO2 is the one which the patient is alert and comfortable on – pH can guide to acute or chronic hypercarbia Evidence

• Systematic review of non-invasive positive pressure ventilation for chronic . AU Hannan LM, Dominelli GS, Chen YW, Darlene Reid W, Road J SO Respir Med. 2014;108(2):229. • BACKGROUND: This systematic review examined the effect of non- invasive positive pressure ventilation (NIPPV) on patient reported outcomes (PROs) and survival for individuals with or at risk of chronic respiratory failure (CRF). • METHODS: Randomised controlled trials (RCTs) and prospective non-randomised studies in those treated with NIPPV for CRF were identified from electronic databases, reference lists and grey literature. Diagnostic groups included in the review were amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), Duchenne muscular dystrophy (DMD), restrictive thoracic disease (RTD) and obesity hypoventilation syndrome (OHS). Evidence

• RESULTS: Eighteen studies were included and overall study quality was weak. – ALS/MND had improved somnolence and fatigue as well as prolonged survival with NIPPV. – OHS, improvements in somnolence and fatigue, dyspnoea and sleep quality were demonstrated, while for – RTD, measures of dyspnoea, sleep quality, physical function and health, mental and emotional health and social function improved. – There was insufficient evidence to form conclusions regarding the effect of NIPPV for those with DMD.

• CONCLUSIONS: This review has demonstrated that NIPPV influences PROs differently depending on the underlying cause of CRF. These findings may provide assistance to patients and clinicians to determine the relative costs and benefits of NIPPV therapy and also highlight areas in need of further research.

Acute CO2 Retention Syndromes

CO2 REMOVAL IN VENTILATION Acute CO2 Retention

• AE-COPD • Acute Severe Asthma • Due to neurological conditions /drugs – Consider OP/NP airway or ETT for airway patency

– NIV or ETT as per clinical status rather than CO2 level

– No validated cut-off for CO2 level or rate of rise of CO2 to guide intubation – On A-C Ventilation: Target mild alkalosis / hypocapnea • Obstructed Tracheal Tube: Correct appropriately Ventilation & CO2 in AE-COPD

• NIV-Standard mainline treatment

– Based on symptoms & not on CO2 • Intubation for failed NIV

– Respiratory fatigue rather than CO2 level – Use spontaneous modes if feasible • Avoid rapid correction of chronic hypercarbia when using Assist-Control Ventilation

– Acute (metabolic) alkalosis with high HCO3 – Acute hypokalemia acute arrhythmias • COPD (between exacerbations)

– NIV as per symptoms not CO2 – Role of day/night time or long term “elective” NIV unclear

NIV in COPD Lightowler. Et al Meta-Analysis BMJ 2003

Composite End point: Mortality, ETT, Intolerance to Rx NIV in COPD Lightowler. Et al Meta-Analysis BMJ 2003

Mortality Risk for intubation Acute Severe Asthma

Anaesthesia and Intensive Care. 1991;19:119 Circulatory Arrest Induced by Intermittent Positive Pressure Ventilation in a Patient with Severe Asthma

• 36-year-old woman with asthma since childhood – The patient presented by ambulance with acute severe asthma after three days of worsening dyspnoea and wheeze. • Twenty-five minutes after presentation, she was intubated • Hand ventilation was commenced by an anaesthetist experienced in these techniques at a rate of 14/min and an estimated tidal volume of 600-700 ml. – The Sp02 initially increased to 94%. – However, the started to fall – Five minutes after intubation BP was unrecordable.

Circulatory Arrest Induced by Intermittent Positive Pressure Ventilation in a Patient with Severe Asthma

• External cardiac massage was commenced and IPPV was continued at the same rate and tidal volume. – The patient was given 0.5 mg of intravenous adrenaline, – 8 mg of intravenous pancuronium – 1000 mcg of salbutamol via the endotracheal tube. • During the next fifteen minutes of cardiopulmonary resuscitation the patient remained in apparent electromechanical dissociation, with sinus rhythm on the electrocardiograph monitor and no evidence of cardiac output. – Received 3 mg adrenaline. Circulatory Arrest Induced by Intermittent Positive Pressure Ventilation in a Patient with Severe Asthma

• Twenty-five minutes after intubation the situation was considered irretrievable. External chest compression and ventilation were ceased and the endotracheal tube was disconnected from the ventilation bag. • Three minutes after cessation of treatment heart rate had increased to 115/minute (sinus rhythm). Five minutes after treatment had ceased, carotid and femoral became palpable although the blood pressure was still unrecordable. Circulatory Arrest Induced by Intermittent Positive Pressure Ventilation in a Patient with Severe Asthma

• Ventilation was recommenced at a rate of fifteen breaths per minute and within fifteen seconds the carotid was again impalpable. • Ventilation was reduced to a rate of six to eight per minute, with a short inspiratory phase and a prolonged expiratory phase. Within three minutes the pulse rate was 150/ minute (sinus rhythm) and the systolic blood pressure returned to 110 mmHg. Circulatory Arrest Induced by Intermittent Positive Pressure Ventilation in a Patient with Severe Asthma

• When ventilation was transiently increased on three subsequent occasions to rates greater than ten per minute, the blood pressure became unrecordable on each occasion. • Seventy-five minutes after initial intubation the blood pressure was 165/80 mmHg, the pupils were reactive to light, and the patient was starting to move spontaneously. Circulatory state remained satisfactory without the need for volume expansion or support. • The patient subsequently showed satisfactory resolution of asthma. Severe cerebral ischaemic damage was initially present • By six months she was functioning independently at home with minimal persisting neurological deficit.

Mechanical Ventilation in Severe Asthma Mechanical Ventilation in Severe Asthma

• With recognition of danger of PEEPa, ICU mortality has decreased • Review of 1223 ventilated asthmatics – 80% deaths associated with CPR prior to ICU – Crit Care Med 2004;8:R1112-21 Role of NIV in Asthma

• Five studies have reported on the use of NIV for patients with asthma who had persistent hypercapnia or excessive work of breathing despite treatment with bronchodilators and corticosteroids. • Only 19 / 112 patients required intubation. CO2 Removal in Acute Asthma • In Acute severe asthma, the risk of PEEPa is greater than that of hypercarbia

– It is acceptable to target a lower CO2 as long as there is no increase in PEEPa  hemodynamic worsening – May have to compromise if CPR has previously occurred & patient not recovered consciousness

• PaCO2 should not be used to decide about intubation – Apnea or Unresponsive – Progressive fatigue despite maximal medical therapy – Failed trial of NIV ARDS

CO2 REMOVAL IN VENTILATION Permissive Hypercarbia in Asthma & ARDS

• Widespread appreciation of risks of mechanical ventilation & role of permissive hypercapnia in acute asthma – Understanding that mechanical ventilation requires trade offs between various parameters • Growing appreciation of the baro-trauma, volu- trauma or stretch-trauma in ARDS – Baby lung & Sponge lung • The concept of protective ventilation – Gentle ventilation – Low Tidal volumes & airway pressure ARDS: Pathophysiology Insights ARDS & Hypercarbia

• The underlying pathophysiology of shunt & V/Q mismatch does not usually cause CO2 retention as hyperventilation will clear the CO2 from the normally functioning lung

• High CO2 in a self ventilating patient is a sign of impending fatigue

• High CO2 in a ventilated patient is a sign of a severe ARDS • Hypercapnea in ventilated ARDS is an independent predictor of a poor outcome ARDS & Permissive Hypercarbia

• Hickling KG Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hypercapnea in severe adult respiratory distress syndrome. Intensive Care Med 1990;16:372-7 • Retrospective analysis of 50 patients with Severe ARDS

– SIMV: Low Pressures, TV and Min volumes regardless of CO2

– Mean max PaCO2 = 62 mmHg, Highest CO2 = 129 mmHg • SMR Actual vs predicted (APACHE II) mortality 16.0/39.6% • Mortality 2/ 10 in subgroup with ~ 100% predicted mortality (ventilator score > 80) • We suggest that this ventilatory management may substantially reduce mortality in ARDS, particularly from respiratory failure.

ARDS: The Definitive Trial (N Engl J Med 2000;342:1301-8) • TV: 12 ml/kg PIP < 50 vs 6ml/kg & PIP < 30 – Lower mortality: 31% vs 39.8%, P = 0.007 • Five basic components – Volume Control Ventilation (Any mode but target TV) – Low tidal volume • 6 ml/kg ideal body weight – Low plateau airway pressure

• < 30 cm H2O – Simultaneous escalating of FIO2 & PEEP • Prevent hypoxemia – Avoidance of hypercarbia & acidosis • Increase Respiratory Rate

• Correct acidosis with HCO3

ARDS & Permissive Hypercarbia

• "ARTERIAL pH and PaCO2 / EtCO2 Goal: pH = 7.30 – 7.45 – Leave the respiratory rate at the current settings • Acidosis management: pH 7.10 – 7.30 – Increase ventilator rate until pH > 7.30 or PaCO2 < 25 – Maximum set ventilator rate is 35 bpm • Acidosis Management: pH < 7.10 – Increase the set ventilator rate to 35 bpm • If pH remains < 7.10, tidal volume may be increased in 1ml/kg IBW steps until pH > 7.10 ARDS & Permissive Hypercarbia

• Mortality ARDS-Net: 31% • Default setting in control arm of subsequent trials – Very low mortality: 27.5-31.5% • Given this low mortality (in RCTs) it is sensible to use the whole ARDS-Net protocol as the default strategy for ventilating ARDS – Hypercapnea should be avoided, but not at the cost of high TV or airway pressure The PHARLAP Study (ANZICS-CTG)

• Permissive Hypercapnia, Alveolar Recruitment and Low Airway Pressure • Pilot: Critical Care 2011, 15:R133 – This study examines the effectiveness and safety of a novel open lung strategy, which includes permissive hypercapnia, ……….. – This open lung strategy was associated improved oxygenation and lung compliance over seven days • RCT: ClinicalTrials.gov Identifier:NCT01667146 – Currently recruiting patients

ECMO & ECCOR

• ECMO ? Positive trial (CESAR) – ICUs with ECMO option have better outcome • ECCOR: No definitive trial – Critical Care 2014, 18:222 Extracorporeal removal for patients with acute respiratory failure secondary to the acute respiratory distress syndrome: a systematic review – Evidence for a positive effect on mortality and other important clinical outcomes is lacking. • Practical options but need experienced centers or in the context of RCTs Conclusions

• CO2 is very tightly controlled physiologically & variations are poorly tolerated and rapidly corrected

• CO2 management with mechanical ventilation occurs in various clinical settings – Generally target a mild hypocarbic alkalosis • Chronic hypercapnia syndromes – Spontaneous and non invasive modes preferred

– Target symptoms not CO2 levels – Home BiPAP improves quality of life, daytime symptoms and may decrease CAD & CCF Conclusions

• In acute hypoventilation, NIV or ETT + ventilation till situation reserved • In severe acute asthma, target PEEPa and hemodynamic parameters and not normocarbia – Unless CPR has occurred • In ARDS try to maintain normal pH but not at cost of high TV or PAP – Consider Extracorporeal options Concluding Thought

Is CO2 Removal an Important goal in Ventilation? Yes (& No)

Always, treat the patient and not the number