Variation in Definition of Prolonged Mechanical Ventilation

Discussion

In this scoping review, we identified substantial variation in the application and definition of terms a priori hypothesized to describe mechanically ventilated subjects no longer in the acute phase of mechanical ventilation. Duration of mechanical ventilation was a common defining criterion; however, there was lack of agreement across included studies as to the number of consecutive days (or hours) that patients should require mechanical ventilation to meet cohort inclusion criteria. More than half of the included studies did not provide a rationale for their chosen definitional criteria of cohort terms used, meaning that the reasoning behind selection of these terms and their criteria was unclear. Inclusion of a large number of studies with heterogeneous study designs and study objectives resulted in the identification of numerous reported study outcomes. Additionally, we identified variability in the criteria used to define weaning and/or extubation success, specifically the duration of monitoring subsequent to liberation from mechanical ventilation during which the subject did not require further invasive or noninvasive support.

Some of the identified heterogeneity in the duration of ventilation used as definitional criteria for subject cohorts may be due to characteristics of the study region. For example, use of ≥ 21 d was most common in Asian countries, particularly Taiwan, where this criterion is used to step patients down to a lower level of care.¹³ Twenty-one days is also used as a trigger for transfer to long-term acute care in the United States¹⁴; however, only 17 long-term acute care studies from 187 United States studies were identified in this review. The duration of mechanical ventilation used as a defining criterion was also influenced by inclusion of surgical only versus a mixed study population. The longest duration used in studies of surgical subjects was ≥ 15 d compared with a maximum of >1 y in heterogeneous cohorts. Furthermore, the inclusion of studies using various data sources (direct observation vs administrative databases) may have generated heterogeneity. Data collection from an administrative database requires the use of codes, such as the ICD code 96.72 indicative of ≥ 96 h of mechanical ventilation, to identify a patient population, whereas prospective studies can use any criteria considered appropriate by the investigator team.

There is little doubt that there is a distinct cohort of relatively low-volume, high-cost, and poor outcome patients requiring mechanical ventilation for longer than the average ICU patient.^15–19 In 1989, Wagner et al²⁰ identified that 6% of a cohort of nearly 4,000 ICU subjects were ventilated for ≥ 7 d and consumed 37% of ICU costs, suggesting that this is not necessarily a new phenomenon solely due to advances in technology or worsening population comorbidity. However, our data suggest that we are far from understanding whether study cohorts are referring to similar patient phenotypes within or across studies and far from establishing consensus on how to define this cohort. Using terms such as chronic or persistent critical illness, several studies have documented a syndrome of persistent organ dysfunction characterized by profound weakness and extreme symptom burden.²¹ Such terms may have merit when trying to distinguish subject cohorts within the spectrum of critical illness; however, while also suffering from lack of consensus, some authors believe this term encompasses patients without a concomitant prolonged need for mechanical ventilation. Conversely, patients such as those with established neuromuscular disease may require prolonged to indefinite mechanical ventilation and not meet other definitional requirements of chronic critical illness.²²

Lack of consistency as to the number of consecutive days (or hours for surgical patients) used as definitional criteria suggests that this may be a rather arbitrary marker and may not be the best criterion to identify transition from acute to PMV and a concomitant review of goals of care. Indeed, using Delphi methods and a 38-member expert panel to establish the criteria that should define the transition from acute care to PMV, our group identified that the number of consecutive days of mechanical ventilation was one of 6 (out of 20) defining criteria that did not gain consensus.²³ Preferred criteria were patient stability from a physiological perspective, repeated unsuccessful attempts at weaning, and the patient's wishes to remain ventilated. These criteria reflect transition from the acute phase of critical illness and an estimation of weaning difficulty as reflected in the simple, difficult, and prolonged weaning classifications proposed in 2007.²⁴ These weaning classifications may be more useful than terms such as PMV not only because they incorporate an element of weaning difficulty but also because they provide an objective marker that weaning attempts have been commenced. What is missing from these classifications, warranting further consideration, is when to classify a patient as unweanable.

We found that definition of the time period in which determination of weaning and/or extubation success occurred was highly variable, ranging from 6 h to 28 d. The NAMDRC definition suggests that PMV patients should only be considered successfully weaned when able to maintain spontaneous breathing without invasive or noninvasive ventilatory support for a minimum of 7 d.⁸ Rationales for monitoring over 7 d for the need to reestablish mechanical ventilation included the potential for slower recovery of the respiratory system and the likelihood of more chronic comorbidities in this patient population. Additionally, some authors have suggested that the need for reestablishment of mechanical ventilation after 3 d is most likely due to a new or unrelated process.²⁵ However, from a patient and health-care system provider perspective, no further requirement for mechanical ventilation enabling discharge from the admitting unit is a more useful definition of weaning and/or extubation success because it demonstrates recovery and the ability to transition to a lower-acuity and therefore lower-cost care location.

Few studies included in this scoping review commented on the inclusion of noninvasive ventilation after discontinuation of invasive support when defining weaning success. The role of noninvasive ventilation is an important element for consideration for this definition,²⁴ particularly in view of increased utilization in recent years.²⁶ A Cochrane systematic review²⁷ found that the use of noninvasive ventilation as a weaning strategy to enable extubation for subjects with the potential to wean, but not yet able to tolerate mechanical ventilation discontinuation, demonstrated decreased weaning failure, mortality, ventilator-associated pneumonia, ventilation duration, and ICU length of stay compared with weaning strategies that did not include noninvasive ventilation. Failure to consider the use of noninvasive ventilation after extubation when pooling data from studies that do or do not use an early extubation to noninvasive ventilation approach will produce inaccurate estimates of weaning success.

We identified 39 distinct study outcomes reported by ≥ 3 included studies, with stay, mortality, and mechanical ventilation duration described by over one third of studies. Previously, our group has identified substantial variation in the selection and definition of outcomes among trials of interventions hypothesized to influence mechanical ventilation duration.²⁸ Initiatives such as the Core Outcome Measures in Effectiveness Trials (COMET) group aim to facilitate the development and application of agreed standardized sets of outcomes, referred to as core outcome sets.²⁹ Numerous critical care professional societies have called for standardization in the reporting of study end points and a standard set of outcome measures with several core outcome set development projects related to critical care under way.³⁰ However, such initiatives are relatively recent. Our data can be used to inform such a project that can then be used in future studies of patients experiencing PMV. Without strategies to gain consensus, known variation in the selection and measurement of outcomes of studies recruiting mechanically ventilated patients combined with variation in subject cohort definitions, as identified in this scoping review, will continue to drive inconsistency and limit interpretation of study findings.

Classification of homogeneous cohorts of mechanically ventilated subjects experiencing critical illness using clear definitional criteria is important. Prognostication, care goal setting, implementation of effective therapies, or conversely conversations around limitation of therapy may be limited due to a failure or delay in recognizing patient transition from acute care to PMV.^23,31 Additionally, clear definitions are required for successful conduct of further research, including enrollment of subjects with a similar phenotype into clinical trials, epidemiological studies, and meta-analyses.^32,33 Our data suggest that further consensus work is required to classify these cohorts, considering defining features in addition to the duration of mechanical ventilation. Such consensus work is likely to result in a set of terms as opposed to a single term to describe the patient spectrum.