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

2. 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

3. 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

4. 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:
N Engl J Med 1995; 332:
Re-intubation rates average~15%
*AJRCCM 1999;159:

5. All attempts are
NOT likely to succeed!!

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

7. 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:
N Engl J Med 1995; 332;

8. “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

9. 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:
* Eur Respir J 2007; 29:
“Prolonged Ventilation”

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

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

12. 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.

13. 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

14. 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:

15. 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:

16. 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:

17. 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:

18. 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

19. 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.)

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

21. 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:

22. 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:

23. 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

24. Fluid Restriction (FACTT)
Achieved 7-day fluid balance of
ml (conservative) vs 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:

25. 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:
PaOP and plasma protein conc. have value?
AROC= 0.93 ± 0.04
Critical Care 2010; 14: 211

26. 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: CCM 2009; 37:

27. 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

28. 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

29. 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 )
Cut-off of 275 pg/ml
Questionable incremental value*
AJRCCM 2012: 186;
*Critical Care 2010; 14: 211

30. 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

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

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

33. ARDSnet: W-3 Fatty Acids
JAMA 2011; 306:

34. 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?

35. 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:
CC Clin 1991; 7:

36. 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…..

37. 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: )

38. 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:
Cochr Databa of Sys. Rev. 2014, DOI: / CD
pub3.
Meta-analysis RR: 0.65 (95% CI; )

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

40. 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

41. 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:

42. 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:
*AJRCCM 2012; 185:

43. 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

44. 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

45. Is there evidence? 5 RCT studies identified 406 patients Defn.
Bouderka 2004, n= d
Dunham 1984, n= d
Rodriguez 1990, n= d
Rumbak 2004, n=120 <2 d
Saffle 2002, n=44 ASAP
BMJ 2005; 330: 1243

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

47. Recent Tracheostomy RCTs
Italian* TRACMAN**
(Terragni et al)
Early Late Early Late N
Day of trache
% trached 69% % % %
Mortality No difference No difference
VAP HR: 0.66; NS N/A
ICU LOS K; HR: 0.73 ( ) 13 days; NS
Ventilation duration K; HR: 0.70 ( ) N/A
*JAMA 2010; 303:
**JAMA 2013;309:

48. 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…….

49. 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 ( )
p=0.05
Ventilator-free days

50. 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.

51. Simple Wean by Protocol
300 patients randomised
Adjusted RR of extubation
with Protocol was
2.13 (95% CI = )
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: )
N Engl J Med 1996; 335:

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

53. 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