Difficult Weaning An approach Ram E. Rajagopalan, MBBS, AB (Int Med) AB (Crit Care) Head, Department of Critical Care Medicine SUNDARAM MEDICAL FOUNDATION Chennai

Goals of this talk To define “difficult” wean Evaluate the pathophysiology of ventilator dependence Identify difficult-to-wean groups Consider a systematic approach to minimising reversible causes of ventilator dependence Consider methods to enhance wean Not an evaluation of long-term ventilator dependence

What is weaning? Objective “readiness” criteria: “Discontinuation”; the apolitical term It starts when the doctor decides that the disease has resolved & patient is “ready” for K support Objective “readiness” criteria: Adequate oxygenation (P/F > 200, PEEP<5) Stable CVS (BP, ’pressors, HR) Adequate cough reflex Adequate mentation (GCS>12) ? Rapid-shallow breathing index <100 Chest 2001; 120:375S–395S

Initial Trial of Discontinuation When patients are “ready” to wean, a spontaneous breathing trial (SBT; using a T-piece for 2 hours) is tolerated by most. Abbreviation to a 30-min SBT reduces ICU & Hospital LOS* AJRCCM 1994; 150: 896-903 N Engl J Med 1995; 332: 345-50 Re-intubation rates average~15% *AJRCCM 1999;159:512-518

All attempts are NOT likely to succeed!!

Spanish Collaborative Trial Approach to the failed SBT N Engl J Med 1995;332; 345-50.

Summary Approach The Failed SBT After return to MV, patients should undergo a daily 2-hour T-piece trial PS(7 cm H20) + PEEP is acceptable IMV should NOT be used AJRCCM 1994; 150: 896-903 N Engl J Med 1995; 332; 345-50.

“Weaning” vs. “Extubation” Success Success with and SBT / RSBI is Neither specific (false +ve; fail extubation) 15% re-intubation rate Nor sensitive (False –ve; prolonged vent) Difficult to study Extrapolate from spontaneous extubation High success even after failed tests

Defining “Difficult-to-wean” Consensus Definitions* “Difficult Wean” In acute cases ~25-40 % & need ~ 7days & 3 SBTs “Prolonged Wean” Up to 14 days (~10%) “Prolonged Mechanical Ventilation” (PMV) is the need of MV >21 days for >6 hours /day; 3-7% J Mortality / Resource use “Ready to wean” Initial T-piece SBT 2/3 extubated (15% reintubation) 1/3 fail Daily SBT/ Pres. Sup 85-90% weaned in 14 days AJRCCM 2001; 164: 186-7 * Chest 2005; 128: 3937-54 * Eur Respir J 2007; 29: 1033-56 “Prolonged Ventilation”

Weaning Difficulty & Outcome Frequency ■Simple ■Difficult ■Prolonged Re-intubation Mortality AJRCCM; 2013: 187; 1294-1302

Pathophysiology Rapid shallow breathing ? Response to inadequate drive / breath ? Inappropriate response to increased load N Engl J Med 2001; 344: 1986-96 Chest 2001; 120:375S–395S

Pathophysiology Rapid shallow breathing (K RR D in COPD) Increased respiratory load Higher PEEPi Higher Elastance Higher Resistance Maintained neuromuscular drive (P0.1)* Reduced muscle strength (Pdi max)* Imbalance between load & capacity Higher PCO2 Similar in COPD and post-CTS* Not predictable by baseline mechanics * AJRCCM 2000;161: 1115–23.

Effect of weaning on CV Pulmonary Spontaneous breathing hypertension RV Failure Spontaneous breathing K intrathoracic pressure (J insp. Swings) J Venous return Hypoxia Venous desaturation Unmasks LV Diastolic Dysfunction Pulmonary edema Anesthesiology 1988; 69:171–179 AJRCCM 1998;158:1763–1769. Chest 2001; 120:375S–395S

are stupid if you still want to read Reversible Factors Improve neuromuscular competence Treat Sepsis Nutritional support without overfeeding Replace K, Mg, P to normal Assure periods of respiratory muscle rest; avoid exhausting breathing trials Limit use of neuromuscular blocking drugs Consider stopping aminoglycoside therapy Consider Neurological disease Hypothyroidism Over sedation Critical illness myopathy / polyneuropathy Steroid myopathy Investigational / unproven Anabolic Steroids Growth Hormone Aminophylline Reduce respiratory load Resistance Bronchodilators Corticosteroids Removal of airway secretions Treatment of upper airway/ET obstruction Compliance Treat Pneumonia Treat pulmonary oedema Reduce intrinsic PEEP Drain large pleural effusions Evacuate pneumothoraces Treat Ileus Decompress abdominal distension Ve Treat sepsis Antipyretics Avoid overfeeding Correct Metabolic acidosis Bronchodilators Maintain least PEEP possible Resuscitate shock and hypovolemia Identify and treat pulmonary embolism I think you are stupid if you still want to read the whole list! A (c)heck list !! From: Chest 1998; 114: 886-901

Risk Factors: Influence of Aetiology COPD 39% weaned 59% weaned NEURO 62% weaned Ac. Resp. Failure f/Vt <100; MIP < -20 2-hour T-piece trial AJRCCM 1998; 158:1855-62.

Influence of Aetiology COPD 39% weaned 59% weaned NEURO 62% weaned Ac. Resp. Failure f/Vt <100; MIP < -20 2-hour T-piece trial 9% re-intubated 36% re-intubated Low GCS AJRCCM 1998; 158:1855-62.

Weaning Risk; Co-morbidity >1400 patients in 23 LTC facilities Mean age =72 years High frequency of associated co-morbidity COPD, CAD & Neurological Dx Renal failure; 1.9X probability of failed wean GCS <8 ; 6.5X probability of weaning failure AJRCCM 2003; 167: A458 Chest 2005; 128: 3937-54

Other Risk Factors Age >65; comorbidity APACHE Score Neurological failure COPD / J Secretions / Feeding (CO2 retention at SBT) Respiratory failure of Cardiac Origin (J BNP / K ScvO2 at wean) Critical Illness Polyneuropathy Nutrition

Neurological Function Neurological drive is well preserved in most difficult-to-wean patients Drive may be suppressed by CVA Non-convulsive seizures Electrolyte disturbance (Low Na) Medication (sedatives) Hypothyroidism (+ impairs muscle fn.)

Sedation: Daily Discontinuation RCT; 128 adults on ventilation “Wake-up” call Routine Sedation Daily d/c N Engl J Med 2000;342:1471-7.

Hypothyroidism is a rare but PMV & Hypothyroidism 140 patients with PMV (routine screen) 1 old hypothyroid TSH h in 16 (12.1%) TSH h+ K T3/ T4 = 4 (3%) Clinical suspicion, BMI are poor correlates. Hypothyroidism is a rare but treatable cause of PMV Chest 2004; 126:1307 - 12

Predictors of Wean Aetiology matters COPD / ARF Neurology Duration of ventilation Age f / Vt ratio P0.1 MIP Neurology MEP f / Vt . P0.1 AJRCCM 1998; 158:1855-62.

Cardiovascular Reserve Weaning causes significant changes in LV & RV function Consider occult coronary disease Beta blockade? Optimise function Weight loss associated with diuresis correlates with wean in PMV* My bias towards nitrates Dobutamine unlikely to be beneficial Inodilators (enoximone) used effectively in CVTS * AJRCCM 1992; 145: A522

Fluid Restriction (FACTT) Achieved 7-day fluid balance of -136+490 ml (conservative) vs. 6992+502 ml K Pplat & oxygenation index ________________________________________ Expected D in ’lytes __________________________________________ 2 day J vent-free & ICU-free days (p <0.001) ______________________________________________ No D in mortality N Engl J Med 2006;354:2564-75

SvO2 monitoring in wean PaOP and plasma protein conc. have value? Venous desaturation was significantly K in patients who fail weaning (SBT) AROC: 0.70 ± 0.08 AJRCCM 1998; 158: 1763-69 PaOP and plasma protein conc. have value? AROC= 0.93 ± 0.04 Critical Care 2010; 14: 211

Weaning Failure Basal measurement of E/E’ has been validated as a marker of weaning failure in multiple studies; Lamia; E/E’ >8.5 with E/A .0.95; Sens 82% Spec 91% Papanickolaou E/E’ >7.8 Sens 79% Spec 100% ICM 2011; 37:1976-85 CCM 2009; 37: 1696-1701

Weaning Failure & Diastolic Dysfunction Basal E/E’ 10 min E/E’ 1-specificity Sensitivity 68 unselected pts. 28 fail wean Weaning failure if: Basal E/E’ >12.6 (AUC .75) 10min SBT E/E’ >14.5 (AUC .86) Or E’ <8 at baseline Moschietto et al. Critical Care 2012, 16:R81

Implications on Weaning Identification prior to / early in SBT gives room for preventive care If identified; attention to fluid management may enhance weanability May identify a role for NIV / CPAP after extubation

BNP- directed wean RCT of BNP to guide fluid Rx (n=304) 15% CAD 25% COPD 60% neither Avg. P/F = 210 Larger -ve balance (-2.3L vs -0.1 L) Wean time K; 42 hr. vs. 58 hr. BNP J with failed SBT (AROC 0.89 + 0.04) Cut-off of 275 pg/ml Questionable incremental value* AJRCCM 2012: 186; 1256-63 *Critical Care 2010; 14: 211

Respiratory Load Remember: rapid shallow breathing is effective for energy utilisation but affects lung mechanics Increased resistance and elasatance occurs in most difficult weans Minimising load is useful: Lower Ve Sepsis Fever Overfeeding

Nutrition & Respiratory Load OVERFEEDING J CHO:FAT VCO2 LUNG DISEASE COPD PCO2 WEAN FROM VENTILATOR

Overfeeding & Respiratory Load VCO2 is affected more by hypercaloric feeding than by the carbohydrate: fat ratio Chest 1992;102:551-5

ARDSnet: W-3 Fatty Acids JAMA 2011; 306: 1574-81

Motor Function Muscle weakness may be a reversible contributor to ventilator dependence Identify & Rx: Electrolyte problems: Deficiency of K, Mg, P Identify: Critical Illness Polyneuropathy Stop: neuromuscular blocking agents Stop: aminoglycosides Stop: steroids?

Hypophosphatemia Causes are multifactorial Refeeding Syndrome (associated hypo K and hypo Mg) Respiratory Alkalosis / correction of respiratory acidosis Met. alkalosis causes smaller change Sucralfate Used for stress ulcer prophylaxis P repletion improves Pdi CCM 1989; 17: 1115-20 CC Clin 1991; 7: 201-14

Critical Illness Polyneuropathy In one study 96% of patients ventilated >7 days Had EMG/ Biopsy evidence of neuro/myopathy 62% with similar findings in PMV Sepsis may contribute to CIPN Use of steroids, NMB agents of importance in myopathy…..

Glycemic Control The dose-response relationship: k Invasive medical devices are a major cause of preventable infections in hospitals. Intravenous catheters, arterial catheters, urinary tract catheters, endotracheal tubes, and many other devices increase the risk of hospital-onset infection in all patient populations. Based on the estimated number of central venous catheters used each day and typical infection rates, approximately 80,000 catheter-associated bloodstream infections occur in ICUs each year in the United States; the total number of these infections in all areas of the hospital is estimated to total 250,000 each year. (Kluger DM, Maki DG. The relative risk of intravascular device related bloodstream infections in adults. Abstracts of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy 1999:514). The estimated attributable mortality for catheter-associated bloodstream infections ranges from 0% to 35%, depending on study design. The estimated attributable cost per bloodstream infections ranges from $34,508 to $56,000, and the annual cost of caring for infected patients between $296 million and $2.3 billion. Data support patient safety impact and costs associated with indwelling urinary tract catheters. (Crit Care Med 2003; 31: 359-66)

Meta-analysis RR: 0.65 (95% CI; 0.55-0.77) Despite recent controversy on the value of strict glycaemic control in medical patients Effect on CIPN seems consistent…. Chest 2007; 132: 268-78. Cochr Databa of Sys. Rev. 2014, DOI:10.1002/14651858.CD006832. pub3. Meta-analysis RR: 0.65 (95% CI; 0.55-0.77)

Strategy #1 NIV: To Hasten Wean In COPD patients; 60-day mortality & nosocomial pneumonia show improving trends Ann Int Med 1998; 128: 721-8

p 0.10 p 0.06 COPD: NIV weaning Ann Int Med 1998; 128: 721-8 Chest 2001; 120: 438S-44S Ferrer; AJRCCM 2003;168:70–76 NIV wean is NOT an established strategy in ventilated patients with other aetiologies

NIV: To prevent Re-intubation Effective when used prophylactically in selected cases post-extubation; COPD Elderly >65 High APACHE APE as cause J PCO2 at SBT Sampath S, ESICM abstract 2007 The use of NIV in patients extubated after failing SBT has no value. AJRCCM 2011; 184: 672-79

Strategy #2 PS vs. T-piece in SBT The “spurious”* belief that work of breathing J with an ETT and K consistently on extubation p = 0.02 No difference in LOS, mortality. 63% of T-pieced and 70% of PS patients remained extubated (NS) AJRCCM 1997; 156: 459-46 *AJRCCM 2012; 185: 349-50

PS vs. T-Piece in SBT Wean with low PS may result in false +ve SBT pass In COPD & LVF where extubation is to NIV prefer SBT on CPAP alone (over low PS); may perform better In all other cases T-piece is preferred to estimate success more accurately

Strategy #3 Tracheostomy? Improved comfort of caregiver (Doctor / nurse vs. patient) Airway mechanics Less Resistance Increased turbulence ? benefit on wean duration Chest 2001; 120:477S–481S

Is there evidence? 5 RCT studies identified 406 patients Defn. Bouderka 2004, n=62 5-6 d Dunham 1984, n=74 3-4 d Rodriguez 1990, n=106 1-7 d Rumbak 2004, n=120 <2 d Saffle 2002, n=44 ASAP BMJ 2005; 330: 1243

Weaning From Ventilation 8.5 fewer days on ventilator BMJ 2005; 330: 1243 No VAP or mortality difference

Recent Tracheostomy RCTs Italian* TRACMAN** (Terragni et al) Early Late Early Late N 209 210 455 454 Day of trache 7 14 4 10 % trached 69% 57% 92% 45% Mortality No difference No difference VAP HR: 0.66; NS N/A ICU LOS K; HR: 0.73 (0.55-0.97) 13 days; NS Ventilation duration K; HR: 0.70 (0.56-0.87) N/A *JAMA 2010; 303:1483-89 **JAMA 2013;309: 2121-29

Tracheostomy in India Context-specific differences: High rates of VAP K compliance oral antisepsis with ETT Trache may K VAP more than in the west Very poor patient mobilization with ETT Trache facilitates physiotherapy…….

Physical Therapy in ICU Strategy #4 Physical Therapy in ICU 104 patients <72 hours since ICU admit Expected ventilation >24 hrs Control: 55; Sedation interrupt Activity per doctor’s order 35% 21 days 49; Treatment Planned graded PT/OT 59% 23.5 days Independent at discharge OR: 2.7 (1.2-6.1) p=0.05 Ventilator-free days

Protocols: (C)lean, Mean Guarantees of Success? Strategy #5 Protocols: (C)lean, Mean Guarantees of Success? Does the application of nurse/ respiratory care professional directed weaning trial improve outcome? Removes uncertainty and delays involved with physician-centred decisions.

Simple Wean by Protocol 300 patients randomised Adjusted RR of extubation with Protocol was 2.13 (95% CI = 1.55-2.92) Re-intubation was less frequent: 4% vs. 10% (p 0.04) Cost of ICU care was lower (p 0.03) Similar outcomes reported by Kollef et al. (Crit Care Med 1997; 25: 567-74) N Engl J Med 1996; 335:1864-9.

Protocols in difficult wean Weaned COPD >15 days ventilation 55 “protocol” weans vs. 62 historical controls Low quality evidence AJRCCM 2001;164: 225-30

Summary Care of the difficult-to-wean patient consumes resources Identification of high-risk groups can allow better allocation of these resources Identification and correction of reversible co-morbidity is essential to enhance wean Logical ventilatory strategies may improve success Chest 2001; 120: 425S-437S