Samer Abu-Sultaneh
and Christopher W. Mastropietro
Introduction
Mechanical ventilation is a lifesaving interven- tion that is used to support patients with acute respiratory failure. Mechanical ventilation how- ever is not without risk. Complications such as ventilator-induced lung injury, ventilator-associ- ated pneumonia, prolonged exposure to narcotics and sedatives, airway trauma, and consequent respiratory muscle weakness have been well described in the literature [1–5]. Because of these risks as well as the associated costs of prolonged intensive care unit (ICU) care, one of the most important goals of pediatric critical care teams is to decrease the duration of mechanical ventila- tion while concomitantly avoiding extubation failure. Extubation failure has also been associ- ated with increased duration of mechanical venti- lation, ICU length of stay, ventilator-associated pneumonia, hospital cost, and mortality [6–8]. In contrast to current adult ICU models of care, ven- tilator weaning and extubation readiness assess- ment in pediatric ICU populations has not been standardized [9–11]. We aim to present a sum- mary of recent literature focused on pediatric ventilator weaning and extubation readiness assessment that can be used as the foundation for
the discussions and collaborative research needed to improve our understanding of this crucial issue in pediatric critical care medicine and the even- tual creation of pediatric-specific guidelines.
Definitions
One of the challenges encountered by pediatric critical care teams is the lack of clear definitions for the terms commonly used when discussing pediatric ventilator weaning and extubation readiness.
Ventilator Weaning Versus Extubation Readiness
These two definitions are often used interchange- ably in clinical practice and research. Weaning is the gradual decrease of ventilator support, during which a patient assumes a steadily increasing proportion of the responsibility for effective gas exchange. Extubation readiness assessments, on the other hand, are conducted by placing patients on minimal ventilator support for a predeter- mined period of time to assess their ability to maintain gas exchange spontaneously. Further, the primary goal of ventilator weaning protocols is to decrease the duration of mechanical ventila- tion, whereas extubation readiness assessments aim to minimize the risk of extubation failure.
S. Abu-Sultaneh · C. W. Mastropietro (*) Division of Pediatric Critical care, Department of Pediatrics, Riley Hospital for Children at Indiana University Health, Indianapolis, IN, USA
e-mail: sultaneh@iu.edu; cmastrop@iu.edu
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Extubation Failure
The definition of extubation failure is not consis- tent between the studies. Most studies have used reintubation within 48 h of the first extubation attempt as their definition, though some have included patients who receive noninvasive posi- tive-pressure ventilation (NIPPV) or high-flow nasal cannula (HFNC) as extubation failures. The time frame during which reintubations are con- sidered extubation failures has also varied across studies, ranging between 24 and 72 h after extu- bation [7, 12–14]. To avoid confusion and be able to compare studies in the future, extubation fail- ure should be defined as the need for reintubation for cardiopulmonary distress within 48 h of the first planned extubation attempt. Moreover, the timing of extubation failure can be subdivided into three categories: (1) immediate, occurring less than 6 h after extubation; (2) early, occurring between 6 and 24 h after extubation; and late, occurring between 24 and 48 h after extubation.
The majority of extubation failures however occur within the first 24 h of extubation [7, 12, 13, 15].
Post-Extubation Stridor and Upper Airway Obstruction
Post-extubation stridor signifying upper airway obstruction is one of the more common causes of extubation failure in children. Airflow resistance is inversely proportional to the fourth or fifth power of airway radius. Since children have smaller baseline airways when compared to adults, even minimal edema can cause significant increase in airway resistance and work of breath- ing. Definitive criteria for what constitutes post- extubation stridor have also not been standardized;
rather, it is a clinical diagnosis [16]. Most often, physicians use the presence of audible stridor with respiratory distress requiring therapeutic interventions such as racemic epinephrine, sys- temic corticosteroids, inhaled helium-oxygen gas mixture, or reintubation as a surrogate definition of post-extubation stridor [16, 17]. A more physi- ologic approach using calibrated respiratory
inductance plethysmography and esophageal manometry to identifying upper airway obstruc- tion after extubation and differentiate between subglottic and supraglottic types has been used in a recent study [18].
Ventilator Weaning
The course of mechanical ventilation begins with intubation and can be divided into the following phases:
• Acute or escalation phase: this phase starts with initiation of mechanical ventilation and Case Study
A 12-year-old boy is recovering from septic shock and pediatric acute respiratory dis- tress syndrome secondary to streptococcus pneumoniae pneumonia. The child has spent 7 days on high-frequency oscillation ventilation and then transitioned to con- ventional mechanical ventilation 5 days ago. Ventilator settings have been weaned gradually. Currently, the child is receiving synchronized intermittent mechanical ven- tilation with pressure-regulated volume control (SIMV-PRVC) with the following ventilator settings: tidal volume 8 ml per kg, rate 16 breaths/min, inspiratory time 1.2 seconds, pressure support (PS) 12 cmH2O, positive end-expiratory pres- sure (PEEP) 8 cmH2O, and fraction of inspired oxygen (FiO2) 65%. Chest x-ray shows lung expansion to 10th rib posteri- orly. He is breathing spontaneously with- out distress, and his respiratory rate is 24 breaths/min. His oxygen saturation as determined by pulse oximetry (SpO2) is 100% and end-tidal CO2 (EtCO2) 55 mmHg. A curious pediatric resident on the team asks which ventilator setting should be weaned first, how quickly can the child be weaned, and when can the child be extubated.
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continuing escalation of ventilator support until reaching gas exchange goals.
• Plateau phase: this phase is when gas exchanges goals are met and there is no sig- nificant increase of ventilator settings.
• Weaning phase: this phase starts when the disease leading to respiratory failure starts to improve and gradual decrease of ventilator settings occur.
• Extubation readiness assessment: in this phase patient is placed on minimal ventilator support for a predetermined period of time to assess their ability to maintain gas exchange spontaneously.
• Extubation or liberation from mechanical ventilation: this phase happens after patient passes extubation readiness assessment and then discontinued from mechanical ventila- tion by removal of artificial airway or separa- tion for mechanical ventilation if patient has tracheostomy tube in place.
During the plateau phase of mechanical ven- tilation, clinicians should begin planning the patient’s ventilator weaning strategy.
Standardized strategies to wean off mechanical ventilation in pediatric population are limited.
In general, as a patient’s disease process improves and gas exchange can be maintained, pediatric critical care teams initiate ventilator weaning, usually starting with the most poten- tial injurious ventilator settings (see Chap. 1:
Ventilator Management for Pediatric Acute Respiratory Distress Syndrome). As ventilator support is weaned, the patient is gradually allowed to assume more of the breathing sponta- neously and tolerate reductions in the doses of sedative medications. As the minute ventilation provided by the ventilator is reduced (i.e., venti- lator rate and tidal volume (VT) are weaned), work of breathing and EtCO2 should be moni- tored closely. Additionally, the accuracy of EtCO2 measurements depends on appropriate ventilation-perfusion matching and the absence of leak around the endotracheal tube and within the ventilator circuit. Arterial, capillary, or venous partial pressure of carbon dioxide (PCO2) measurements should be occasionally
checked and compared to EtCO2 measurements during the weaning process.
Pediatric studies showed that manual ventila- tor weaning protocols have the potential to decrease duration of mechanical ventilation [19–
22]. The protocols used in these studies differed in regard to the sequence of parameters weaned and rapidity of which each parameter was adjusted. In addition, some protocols were physi- cian directed, while others were respiratory ther- apist directed, and only a portion of protocols included an extubation readiness assessment [21–22]. An example of a weaning protocol is provided in Fig. 3.1 [22].
Closed-loop ventilation has been proposed as a method of standardizing the ventilator weaning process. In closed-loop ventilation, the ventilator would decrease or increase the PS above a patient’s set PEEP based on mathematical algo- rithms utilizing available information such as the patient’s respiratory rate, VT, and EtCO2. In a small pilot pediatric study, this approach showed a trend toward decreasing the duration of mechanical ventilation without increasing the risk of extubation failure [23, 24]. The effective- ness of closed-loop ventilation is dependent upon the accuracy of input data from the bedside moni- toring devices and ventilator itself, especially VT
[25]. Current closed-loop ventilation protocols also lack the ability to assess and incorporate patients’ work of breathing in their algorithm.
Causes of Ventilator Weaning Failure The causes of ventilator weaning failure can be divided into the following categories: residual lung disease, respiratory muscle weakness, car- diac dysfunction, pulmonary hypertension, fluid overload, and neurologic issues (e.g., sedation, central or peripheral nerve injury, and congenital or acquired neuromuscular disorders).
Respiratory Muscle Weakness
Respiratory muscles, most important of which is the diaphragm, can develop atrophy and
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weakness during the course of mechanical ven- tilation [26–28]. Respiratory muscle weakness can be part of critical illness polyneuropathy/
myopathy and is usually complex and multi- factorial. These factors can be related to the critical illness itself (like brain or spine injury, sepsis, acute respiratory distress syndrome, and burns) but also can be related to disuse, protein catabolism, electrolytes imbalance (especially hypophosphatemia and hyperglyce- mia), and medications like neuromuscular blockers, corticosteroids, and aminoglycosides [29, 30].
For patients who are suspected to have respi- ratory muscle weakness, many intensivists will
use periods of time during which the patient receives only continuous positive pressure (CPAP) with PS from the ventilator. These
“sprints” are employed to strengthen or retrain the respiratory muscles. The duration and fre- quency of CPAP with PS are somewhat arbitrary, at the discretion of the bedside clinician. While these sprints are commonly used in clinical prac- tice, there are no published studies or guidelines on their effectiveness in the pediatric population.
At most institutions, periods of CPAP with PS ranging between 30 min and 2 h are ordered to be performed 2–4 times a day and are discontin- ued early if signs of respiratory distress are observed.
Weaning Phase
Minimal Settings Phase
Spontaneous Mode Phase
Rate PIP FiO2 PEEP
Rate
Wean by 2 q 3 h to
a min of 8 If pH≥7.25 and/or PaCO2/EtCO2 ≤ 50
Wean PIP by 1-2 cmH2O Q3 to min of 25 for ≥ 6mo
Minimum for Vt 8 cc/kg When FiO2 < 50%
When PEEP by 1 cm H2O q 3º to min of 5 to
keep SpO2 > 92%
8 15-25 cm H2O (according to age) titrate to Vt = 8 cc/kg
Change mode to PS or VS to achieve Vt spontaneous = 5-7 cc/kg.
FiO2 and PEEP as above.
21% or baseline 5 cm H2O 15-20 for ≤ 6mo
Wean by 2–5% q 3hr to minimum 21% or to baseline
O2 if chronic lung disease If SaO2 or SpO2 ≥ 90%
PIP* FiO2 PEEP*
*Note: Wean PIP and PEEP simultaneously to
maintain same ∆ P or exhaled VT = 8 cc/kg Fig. 3.1 An example
of a pediatric ventilator weaning protocol. PIP peak inspiratory pressure, FiO2 fraction of inspired oxygen, PEEP positive end-expiratory pressure, PaCO2 arterial partial pressure of carbon dioxide, EtCO2 end-tidal carbon dioxide, SaO2
oxygen saturation, SpO2
pulse oximetry, VT, tidal volume, ΔP difference in pressure, PS pressure support, VS volume support
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Cardiac Dysfunction and Pulmonary Hypertension
Underlying cardiac dysfunction can be unmasked during ventilator weaning. As mean airway pres- sures decrease, left ventricular afterload will increase, and signs and symptoms of cardiac fail- ure may become apparent (e.g., pulmonary edema, decreased urine output, poor peripheral perfusion). In patients with pulmonary hyperten- sion, hypercarbia or atelectasis that can occur as ventilator support is reduced could increase pulmonary vascular resistance and precipitate pulmonary hypertensive crises. In these clinical scenarios, ventilator weaning must be halted, or ventilator support may have to be increased.
Vasoactive support and pulmonary hypertensive therapies should then be optimized before wean- ing is reattempted.
Fluid Overload
Fluid overload is common in critically ill chil- dren. Many children requiring mechanical venti- lation can have increased total body water due to capillary leak, fluid resuscitation, and acute kid- ney injury. Fluid overload will result in edema of the upper airway, lungs, diaphragm and chest wall, all of which impact respiratory dynamics and impair gas exchange. Indeed, recent evidence has associated fluid overload with an increased duration of mechanical ventilation in critically ill pediatric patients [31–34]. Fluid status should therefore be assessed carefully before and during the weaning process using daily weights and meticulous review of daily fluid balance. When fluid overload is thought to be hindering ventila- tor weaning, fluid removal strategies such as diuretic administration, pleural or peritoneal drainage, or renal replacement therapy should be considered.
Sedation Optimization
During mechanical ventilation, pediatric patients commonly require sedative medications to
minimize pain and anxiety, though these medica- tions often decrease their ability to spontaneously breathe during the weaning process. Excessive sedation will lead to prolonged duration of venti- lator weaning [21], yet under-sedation and agita- tion will increase airway trauma and the risk of post-extubation stridor, especially in younger patients [17, 18, 35]. The optimal manner in which this balance is achieved has yet to be deter- mined. At a minimum, sedation should be man- aged carefully during the entire ICU course with a focus on minimizing pain and recognizing and treating delirium (see Chap. 18: Optimizing Sedation in the Pediatric ICU).
Mucociliary Clearance
Impaired mucociliary clearance resulting in an excessive burden of secretions can also detrimen- tally affect ventilator weaning. Impaired muco- ciliary clearance during mechanical ventilation can be caused by decrease of ciliary function due to inflammation; excessive mucus production or increased viscosity of mucous; impaired cough due to immobility, sedation, neuromuscular blockade, and muscle weakness; and the endotra- cheal tube itself. Several pulmonary hygiene therapies are available and commonly provided to mechanically ventilated pediatric patients.
Mucolytics such as nebulized hypertonic saline and dornase alpha may be able to thin endotra- cheal tube secretions and thereby aid in their mobilization. The effectiveness of these therapies in expediting ventilator weaning and decreasing mechanical ventilation duration in critically ill pediatric populations is unclear and requires more investigation [36–38]. Chest physiotherapy (CPT) is also used in mechanically ventilated children with atelectatic lung regions, but it can cause oxygen desaturation, hemodynamic changes, an increase in intracranial pressure, and patient discomfort [39]. Intrapulmonary percus- sive ventilation (IPV), which is a form of airway clearance technique that loosen and mobilize secretions toward the upper airways by delivering mini bursts of gas into the lungs at rates between 100 and 300 breaths per minute, might be an
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effective alternative [40]. Until more data are available, practitioners must weigh the balance of the potential benefits of these therapies against the risks and expense, which includes the resources, personnel, and time necessary to administer these therapies.
Extubation Readiness Assessment in Pediatric ICU
Extubation readiness assessment is a prerequisite for extubation in most modern pediatric critical care, but parameters for this practice have yet to be standardized [41]. Extubation readiness assessment can be divided into the following components: screening for entry criteria into an extubation readiness trial (ERT), respiratory sup- port during the ERT, the duration of ERT, criteria for what constitutes a successful ERT, and antici- pation of post-extubation respiratory support needs.
Screening for Entry Criteria into the ERT
Data from pediatric studies of unplanned extu- bation have reported that up to half of these patients remain extubated [42–44]. These data likely reflect, in part, our ability to support patients with noninvasive respiratory modalities but also likely contain missed opportunities for earlier extubation. Many institutional quality improvement efforts have attempted to address this opportunity by establishing extubation readiness assessment protocols that mandates daily screening to determine in patients meet criteria for entry into an ERT (Table 3.1) [14, 21, 45, 46].
Respiratory Support during the ERT There are three reported ways to conduct an ERT in critically ill pediatric patients: CPAP trials with PS, CPAP trials without PS, and T-piece trials (i.e., oxygen provided without
positive pressure). A survey of pediatric criti- cal care physicians working in the United States found that 95% of physicians use PS augmentation (or simply called PS/CPAP tri- als) during ERTs [41]. A prospective, random- ized study of 257 mechanically ventilated patients comparing a PS-augmented ERT to T-piece ERT showed similar success rates between the two types of ERT and no statisti- cal difference in the rate of extubation failure [47]. In this study, however, entry criteria to initiate an ERT were at the discretion of the attending physician rather than predetermined objective clinical parameters. In other words, clinicians may have had a higher threshold to initiate an ERT in patients who were to be placed on a T-piece, which could have overes- timated the success of T-piece ERT. While current adult guidelines recommend using 5–8 cmH2O of PS [48], the amount of PS to be used in a pediatric ERT is still under debate. In some studies, PS used for the ERT is set based on endotracheal tube size; 10 cmH2O for 3 and 3.5 mm diameter tubes, 8 cmH2O for 4 and 4.5 mm diameter tubes, and 6 cmH2O for 5 mm and larger diameter tubes [14, 21, 45].
Recently published data however has sug- gested that using PS during an ERT underesti- mates post-extubation effort of breathing, regardless of endotracheal tube size, and may contribute to a higher extubation failure rate (Fig. 3.2) [49, 50]. Based on these data, chil- dren who experience any concerning symp- toms (e.g., tachypnea, diaphoresis, tachycardia, increased EtCO2) during an ERT using CPAP with PS are likely at high risk for extubation failure.
Table 3.1 Entry criteria for extubation readiness trial Presence of spontaneous breathing
Adequate cough and gag reflex
No planned procedures requiring general anesthesia within the next 24 h
Cardiopulmonary stability with no increase of vasoactive drips for at least 12 h
No increase of ventilator support for at least 12 h Adequate lung compliance and gas exchange
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Duration of the ERT
The duration of ERTs in pediatric populations has most commonly been reported to be 2 h [14, 21, 35, 45–47]. Though shorter periods of ERT have been used, there is concern that these short trials might mask some respiratory insufficiency.
In a prospective study, a 15 min ERT using CPAP of 5 cmH2O was found to be successful in pre- dicting extubation success [51]. In this study the physicians determined whether or not to proceed with ERTs by their standard clinical assessment which may have delayed initiation of ERTs, rais- ing concerns for selection bias. This may have overestimated the success of such short ERTs.
Criteria for What Constitutes a Successful ERT
The main criteria for passing an ERT is maintain- ing adequate spontaneous gas exchange, which is typically considered to be maintaining an SpO2
within a targeted range (usually ≥92%) with mod- est FiO2 (≤ 0.4), maintaining VT ≥ 5 ml per kg of ideal body weight, and no signs of cardiopulmo- nary compromise. Accurate measurement of VT
depends on the absence of a significant leak around the endotracheal tube or within ventilator circuit and the location at which VT is measured, at the end of ETT vs. at the ventilator [25]. Leak percent- age can be calculated as follows: [(inspired VT – expired VT)/inspired VT) × 100]. Leak percentage less than 20% is required to accurately assess VT.
Level of consciousness or sedation must be adequate to promote spontaneous breathing. As previously discussed in ventilator wean section, both oversedation and under-sedation can con- tribute to failure of an ERT. Tachypnea, tachycar- dia, and diaphoresis often associated with excessive agitation will compromise cardiopul- monary reserve [14]. Use of peri-extubation medications that can keep patients calm without suppressing their respiratory drive can be helpful in this scenario. Specifically, the use of dexme- detomidine has become relatively commonplace at some centers to facilitate extubation readiness assessment and extubation [52]. Subjective assessment of the quantity and quality of endo- tracheal and oral secretions is also required dur- ing an ERT, as an excessive secretion burden, especially in a child with underlying neurologic injury, can lead to extubation failure [41].
Anticholinergic drugs such as scopolamine and
1000
Pressure.Rate Product before and after Extubation All Patients, All endotracheal tube sizes, n=409
Median 25%-75% Non-Outlier Range
800
Pressure. Rate Product
600
400
200
0 Pressure Support CPAP
Condition
5 minutes 60 minutes Fig. 3.2 Pressure rate
product as a function of peri-extubation respiratory support.
(1) Pressure support of 10 over continuous positive airway pressure (CPAP) of 5 cmH2O. (2) CPAP of 5 cmH2O. (3) Spontaneously breathing at 5 min post-extubation.
(4) Spontaneously breathing at 60 min post-extubation
3 Weaning and Extubation Readiness Assessment in Pediatric Patients