CURRENT
OPINION The differential diagnosis for failure to wean from
mechanical ventilation
Jonne Doorduin, Johannes G. van der Hoeven, and Leo M.A. Heunks
Purpose of review
In this review, we discuss the causes for a failed weaning trial and specific diagnostic tests that could be
conducted to identify the cause for weaning failure. We briefly highlight treatment strategies that may
enhance the chance of weaning success.
Recent findings
Impaired respiratory mechanics, respiratory muscle dysfunction, cardiac dysfunction, cognitive dysfunction,
and metabolic disorders are recognized causes for weaning failure. In addition, iatrogenic factors may be
at play. Most studies have focused on respiratory muscle dysfunction and cardiac dysfunction. Recent
studies demonstrate that both ultrasound and electromyography are valuable tools to evaluate respiratory
muscle function in ventilated patients. Sophisticated ultrasound techniques and biomarkers such as B-type
natriuretic peptide, are valuable tools to identify cardiac dysfunction as a cause for weaning failure. Once
a cause for weaning failure has been identified specific treatment should be instituted. Concerning
treatment, both strength training and endurance training should be considered for patients with respiratory
muscle weakness. Inotropes and vasodilators should be considered in case of heart failure.
Summary
Understanding the complex pathophysiology of weaning failure in combination with a systematic
diagnostic approach allows identification of the primary cause of weaning failure. This will help the
clinician to choose a specific treatment strategy and therefore may fasten liberation from mechanical
ventilation.
Keywords
cardiac failure, diaphragm, differential diagnosis, mechanical ventilation, weaning
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Resp rate Edi DPes DPga DPdi PEEPi WOB PaO2 PaCO2
(per min) Vt (ml) (mV) (cm H2O) (cm H2O) (cm H2O) (cm H2O) (J/l) (mmHg) (mmHg)
Succesfull spontaneous breathing trial in a COPD patient despite an increase in PEEPi and WOB. COPD, chronic obstructive pulmonary disease; Edi, electrical
activity of the diaphragm; PaCO2, arterial carbondioxide partial pressure; PaO2, arterial oxygen partial pressure; Pdi, transdiaphragmatic pressure; PEEPi,
intrinisic positive end-expiratory pressure; Pes, esophageal pressure; Pga, gastric pressure; Resp rate, respiratory rate; Vt, tidal volume; WOB, work of breathing.
a
PS ¼ 5 cm H2O, PEEP ¼ 10 cm H2O.
thickness, thickening fraction, and displacement asynchrony [16], and assessment of respiratory
(Fig. 1). Using M-mode ultrasonography, diaphrag- workload [17,18].
matic dysfunction (vertical excursion <1 cm or par- Diaphragm electromyography (EMG) reflects
adoxic movements) was found in 24 of 82 patients neural respiratory drive to the diaphragm. The
who met criteria for an SBT [14]. These patients (processed) EMG signal can be obtained continu-
showed frequent early and delayed weaning ously using commercially available multielectrode
failures. DiNino and colleagues [15] found in esophageal catheters required for neurally adjusted
63 mechanically ventilated patients that dia- ventilatory assist ventilator mode (Maquet, Solna,
phragm thickening fraction above 30% predicts Sweden). The ratio between diaphragm EMG and
extubation success with a sensitivity and specificity tidal volume is called the neuro-ventilatory effi-
of 88 and 71%, respectively. Very recently, it was ciency (NVE). NVE has been shown to identify
proposed that thickening fraction of the diaphragm weaning failure in multiple studies [19–22].
as assessed with ultrasound could be used to detect Evidently, NVE is sensitive to changes in diaphragm
&&
dysfunction [10 ]. Future fields of ultrasonography function as well as a patient’s load of breathing.
application may be detection of patient-ventilator Diaphragm EMG may also be used to monitor
Expiration Inspiration
SC SC
ICS ICS
Dia
Dia
1.6 mm 2.4 mm
Liver Liver
Ultrasonography measurements:
Liver
FIGURE 1. Normal diaphragm ultrasonography. From left-to-right, top-to-bottom: B-mode diaphragm thickness during
expiration, B-mode diaphragm thickness during inspiration, M-mode diaphragm displacement during normal inspiration,
measurements obtained from images. Dia, diaphragm; exp, expiration; ICS, intercostals muscles; insp, inspiration; SC,
subcutis.
respiratory muscle unloading [23], patient-venti- transmitral early diastolic filling velocity (E),
lator interaction [24], and the effect of residual measured by conventional pulsed wave Doppler,
sedation on respiratory drive [25]. In a preliminary the resulting E/Ea ratio closely correlates with left
observation, it was reported that diaphragm EMG ventricular filling pressure [30]. Moschietto and col-
can be used to detect development of fatigue after leagues [29] found in a nonselected population of
extubation [26]. 68 patients, performing an SBT, that the E/Ea ratio
before and during the SBT was higher in the failure
group than in the successful group. In this study, an
Cardiac dysfunction E/Ea ratio during the SBT of 14.5 predicted weaning
The lungs and heart are functionally and anatom- failure with a sensitivity of 75% and a specificity of
ically coupled and therefore transition of assisted 95.8%. It should be recognized that performing
breathing to unassisted breathing has profound ultrasound at the time of weaning failure might
cardiovascular effects that may induce weaning fail- be quite a challenge.
ure. First, during positive pressure ventilation the B-type natriuretic peptide (BNP) and N-terminal
intra-thoracic pressure (ITP) increases during inspi- (NT)-proBNP are cardiac biomarkers secreted by
ration, whereas during unassisted breathing ITP ventricular cardiomyocytes in response to increased
decreases during inspiration as a result of activation ventricular wall stress. Increases in BNP and
of the inspiratory muscles. The decrease in ITP NT-proBNP levels during the SBT are consistent with
during a weaning trial will enhance venous return weaning failure of cardiac origin, in which BNP
&&
by reducing right atrial pressure, end diastolic right performs better than NT-proBNP [31,32 ]. An
ventricular (RV) volume and as such in patients with increase in BNP levels by more than 12% allowed
normal cardiac function increase RV and left ven- diagnosing weaning failure from cardiac origin with
tricular (LV) output, but may result in heart failure a sensitivity of 76% and a specificity of 78%, with
in patients with compromised cardiac function. the pulmonary artery catheter as a reference method
&&
Second, increased sympathic tone (emotional stress, [32 ]. Mekontso Dessap and colleagues [33] showed
hypercapnia, and hypoxemia) may further increase that a BNP-guided fluid management strategy was
LV afterload. Finally, the transition to unassisted associated with a shorter duration of mechanical
breathing puts an elevated load on the respiratory ventilation, especially in patients with left ventric-
muscles, which increases oxygen consumption and ular systolic dysfunction. In conclusion, changes in
as such is a stress to the heart. The final effects of BNP levels are a reliable and feasible alternative to
unassisted breathing on the cardiovascular system the pulmonary artery catheter for diagnosing wean-
are much more complex. We refer to recent studies ing-induced pulmonary edema. A passive leg raising
&
for review [27 ,28]. Table 2 shows the cardiovascular before the SBT has also been suggested to identify
effects of a successful prolonged spontaneous weaning failure patients related to cardiac dysfunc-
&
breathing trial in a typical ICU patient. tion [34]. Recently, Dres and colleagues [27 ] devel-
As an alternative to the pulmonary artery oped an algorithm for management of weaning
catheter, less invasive techniques are currently used failure from cardiac origin.
to identify cardiac failure during a weaning trial.
Transthoracic echocardiography during an SBT can
identify both systolic and diastolic dysfunction [29]. Cognitive dysfunction
With tissue Doppler imaging, myocardial relaxation A serious and frequent psycho-organic disorder in
can be quantified by measuring the early diastolic critically ill patients is delirium. Critically ill
mitral annulus velocity (Ea). In combination with patients with a delirium have a seven times higher
Succesfull spontaneous breathing trial in a COPD patient with a normal cardiavasular response. ABP, arterial blood pressure; BNP, B-type natriuretic peptide; CO,
cardiac output; COPD, chronic obstructive pulmonary disease; CVP, central venous pressure; HR, heart rate; PaO2, arterial oxygen partial pressure; PAP,
pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; SvO2, mixed venous oxygen saturation.
a
PS ¼ 5 cm H2O, PEEP ¼ 10 cm H2O.
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