Prediction of Extubation Success in Myasthenic Crisis Using Bedside Functional Residual Capacity Measurement: A Prospective Feasibility Study/Yatak Basi Fonksiyonel Rezidual Kapasite Ölçümünün Myastenik Krizde Ekstübasyon Basarisinin Tahminindeki Rolü: Prospektif Pilot Çalisma

Headnote

Abstract

Aim: Extubation failure often complicates the recovery phase of a myasthenic crisis (MC). Bedside functional residual capacity (FRC) is a relatively new technique shown to be promising in the improvement of ventilation management in the intensive care unit (ICU), and may have a role in the estimation of extubation success. Since the prediction of extubation success is difficult due to the absence of formally evaluated disease-specific criteria, the appropriateness of any strategy described for non-neuromuscular conditions should be validated for specific neuromuscular diseases such as MC. In accordance, we designed a pilot study to determine thefeasibilityofbedside FRC measurement in the prediction of extubation success in MC and to determine its yield when added to the conventional parameters.

Material and Methods: We prospectively studied the additive value of bedside FRC measurements to predict extubation outcome in 11 MC episodes. The area under the receiver operating characteristic curve (ROC AUC), sensitivity and specificity of all weaning and extubation indices that passed exploratory analysis were determined.

Results: The frequency of extubation failure, defined as the need for reinstitution of ventilatory support within 72 hours of planned endotracheal tube removal, was 55% in this study population, in which all patients met the standard weaning indices indicating safety of extubation. The risk of extubation failure was connected to higher airway pressures (peak inspiratory and plato pressures; PIP and Pplato; ROC AUCs: 0.933 and 0.917), increased gradient of end-tidal C02to arterial CO2 (CO2 gradient; ROC AUC:0.900) and total airway care score (ACS; ROC AUC:0.983), but not to FRC, the simplified acute physiology score (SAPS-II) and the traditional weaning criteria such asthe rapid shallow breathing index (RSBI) and mouth occlusion pressure (P0.1). Although perhaps useful when measurable, the utility of maximal inspiratory/expiratory mouth pressures (MIP and MEP) was also low due to the inability of MC patients to perform the maneuvers required to obtain these parameters. In contrast, FRC measurement was easily attainable at the bedside, with zero risk to the patient and correlated well to the aerated lung volume measured by chest CT (r=0.717).

Conclusion: This preliminary study suggests that bedside FRC measurement is safe and feasible for long-term monitoring of intubated myasthenic patients. Its utility in determining weaning and extubation outcomes requires further studies with larger samples. Standard weaning parameters may not be accurate enough in the prediction of extubation outcome in MC, probably reflecting differences in the pathophysiology of failure of extubation and weaning. As a new semi-objective measurement of pulmonary secretion status, ACS can be helpful in the identification of the risk of extubation failure. (Yogun Bakim Derg 2012; 3:36-42)

Key words: Myasthenic crisis, maximum expiratory pressure, maximum inspiratory pressure, atelectasis, recruitment

Received: 09.06.2012 Accepted: 28.06.2012

Özet

Amaç: Ekstübasyon basarisizligi myastenik kriz (MK) sürecinin siklikla olumsuz etkileyen bir durumdur. Yatak basinda yapdabilen fonksiyonel rezidüel kapasite (FRC) ölçümünün yogun bakimda ventilator yönetimini olumlu yönde gelistirebilecegine dair ön veriler bulunmakla birlikte bu metodoloji ekstubasyonun kaderini ön görme açisindan da yararli olabilir. Formel olarak hastaliga özgün kriterlerinin belirlenmemis olmasi ektübasyonun kaderinin saptanmasini güçlestirdigi için non-nöromusküler hastaliklar için önerilmis olan herhangi bir stratejinin MK gibi nöromuskuler hastaliklar için uygunlugunun validasyonu gereklidir. Bu görüsle dizayn edilen bu pilot çalismada yatak basi FRC ölçümünün fizibilitesi belirlenmis ve konvansiyonel kriterlere ilave edilmesi durumundaki verimi incelenmistir.

Gereç ve Yöntemler: Bu çalismada 11 MK episodunda ektübasyon sonucunun tahmininde yatak basinda elde olunan fonksiyonel rezidüel kapasite (Ingilizcesini akronimi FRC) ölçümünün katkisi araçtmlmiçtir. ROC egrisi altinda kalan alan [ROC AUC], sensitivite ve spesifisite degerlerinin %95 güven araliginin alt limiti tekyönlü analizi geçen parametreler için hesaplanmistir.

Bulgular: Ekstübasyon sonrasi 72 sa at içindetekrar invazif mekanikventilasyona baglanma ihtiyaci 11 episodun 6'sinda (%55) ortaya çikmistir. Bu hastalarin hepsinde klasik ayirma kriterleri saglanmis durumdadir. Ekstübasyon basarisizligi artmis hava yolu basinçlari (Pik Inspiratuar ve Plato basinci- PIP ve Pplato; ROC AUC: 0,933 ve 0,917); artmis alveolo-arteriyel CO2 gradienti (etCO2-PCO2; ROC AUC: 9,900) ve total hava yolu bakim skoru (ACS; ROC AUC: 0,983) ile iliskili iken FRCve bununyanmda SAPS-II, RSBI ve P100 gibi sikkullandan parametrelerle iliskili degildir. Olasilikla ölçüldügünde yararli olan maksimum inspiratuar ve ekspiratuar agiz içi basinçlarinin (MIP, MEP) hastalarin gereken manevralari yapamamasi nedeniyle kullamminm kisitli oldugu görülmüstür. Oysa, FRC hasta basinda hasta için herhangi bir risk olusturmaksizin basarili bir sekilde ölçülebilmekte olup havalanan akciger volümü için tomografi ile yüksek korelasyon göstermektedir (r=0,717).

Sonuç: Bu alaninda bir ilk olan çalismada hasta basinda FRC ölçümünün ve uzun süreli monitörize edilmesinin myastenik kriz olgularinda güvenli ve uygulanabilir oldugu ortaya konulmus olmaktadir. Ayirma ve ekstübasyon kararinda FRC ölçümünün öngörü degerini belirlemek için ise fazla sayida hasta içeren etkinlik çalismalarina ihtiyaç vardir. Bu çalismada tespit edilen diger önemli bir unsur aralarindaki patofizyolojik farkin aslinda biryansimasi olan ayirma kriterlerinin ekstübasyonun öngörülmesinde belirgin pozisyonu olmadigidir. Pulmoner sekresyon durumunun semi-objektif bir göstergesi olarak "Havayolu Bakim Skoru (Airway Care Score) veya benzerlerinin ekstübasyon basarisizliginin öngörülmesindeki ye ri arastirmaya degerdir. (Yogun Bakim Derg 2012; 3: 36-42)

Anahtar sözcükler: Myastenik kriz, maksimum ekspiratuar basinç, maksimum inspiratuar basinç, atelektazi, rekrütman

Gelis Tarihi: 09.06.2012 Kabul Tarihi: 28.06.2012

Introduction

Extubation of patients following weaning from mechanical ventilation initiated due to a myasthenic crisis (MC) is one of the most challenging tasks in neurological intensive care units (NICU). After subsidence of the MC, the extubation failure rate is in the range of 27%-44% (1-3). Extubation failure and re-intubation are associated with significant morbidity and mortality along with a prolongation in intensive care unit (ICU) and hospital length of stay (4). The factors that influence extubation outcome are not well-established in this specific population. In a few retrospective studies, atelectasis has been shown to be the strongest predictor for extubation failure (1,3). Other suggested indicators of poor prognosis are old age, male sex, history and perhaps number of previous MC, duration of intubation >10 days, low pH on arterial blood gas analysis, low forced vital capacity (FVC) and poor cough strength assessed by maximal expiratory pressure before extubation, as well as the presence of pneumonia (1-3, 5).

Atelectasis affects MC negatively by resulting not only in reduced or absent alveolo-capillary gas exchange and increased shunting, but also in the creation of a focus for pulmonary infection. In MC, the causes of atelectasis are various, and include muscle weakness, inability to clear the airway along with insufficient care of oropharyngeal, nasotracheal and tracheal secretions (obstruction atelectasis) and the use of an unnecessarily high fraction of inspired oxygen (FiO2) (absorption atelectasis) (6). Chest radiography is usually used for the diagnosis and daily monitoring of atelectasis, but its sensitivity is low. Computed tomography (CT) is the most sensitive method, but radiation exposure limits its value as a monitoring tool in addition to difficulties related to the transfer of critically ill patients to the CT suite. Therefore, noninvasive and radiation-free methods that can detect changes in lung volume and ventilation distribution at the bedside are of critical importance. New techniques such as electrical impedance tomography and direct measurement of functional residual capacity (FRC) can be useful in this respect (7, 8). Because atelectasis decreases FRC, its bedside measurement and monitoring during mechanical ventilation can guide the clinician in predicting extubation failure. In this study, we first assessed the feasibility of bedside FRC measurements in assessing extubation outcome in a consecutive series of MC patients necessitating invasive mechanical ventilatory (IMV) support. We also assessed the yield of conventional parameters useful in forecasting extubation fate in MC.

Material and Methods

After approval of the study protocol by the Ethical Committee of Hacettepe University, we prospectively studied patients admitted to our NICU with a diagnosis of MC necessitating IMV between October 2008 and September 2011. Post-thymectomy crises and patients with asthma, chronic obstructive pulmonary disease or significant congestive heart failure were not included in the study.

From the initiation of I MV to the weaning period, FRC was measured daily (at least six times per day) with a nitrogen wash-out method as described and standardized by Stenqvist (FRC IN view®, GE Engström Care Station®) (9). The details of the theory and measurement technique can be found elsewhere (10, 11) and are briefly summarized in Box 1. The average and variability (represented as its standard deviation) of FRC and average of FRC values measured on the extubation day were calculated for each patient. In 9 out of the 11 MC episodes, chest CT (Somatom® Emotion Duo or Sensation 16, Siemens, Germany) was obtained at the discretion of the clinical team during the intubation period. Aerated lung, atelectasis and effusion volumes were measured on these CT images. The aerated lung volume calculation was based on fixed density thresholds (lower threshold -1024 HU, upper threshold -200 HU) and semiautomatic segmentation was done using a Syngo® workstation (12). The contours of atelectasis and effusion were outlined and the volume was calculated on the workstation. Total lung volume was calculated as aerated lung compartments + (atelectasis volume + effusion volume).

We followed a standardized protocol for Intubation, weaning, extubation and re-intubation In these patients. All these procedures were predominantly driven by treating neurointensivists. Four sets of criteria were used to assess readiness for weaning (13): a) pulmonary criteria: partial pressure of arterial oxygen (PaO2) >60 mmHg and partial pressure of arterial carbon dioxide (PaCO2) within normal limits or close to baseline level when FiO2 ≤40% and positive end-expiratory pressure (PEEP) ≤5 cmH2O together with a PaO2/FiO2 ratio (PF ratio) >150 and the ability of the patient to trigger Inspiration (by flow mode), which Is quantified further by measuring the airway occlusion pressure (P0.1 or P100); b) hemodynamic criteria: absence of acute myocardial Ischemia (or normal serum troponin level), heart rate (HR) <140 beats per minute (bpm) and systolic blood pressure (BP) >90 mmHg with no or minimal vasopressor support; c) adequate level of consciousness as quantified by the Glasgow coma scale (GCS); d) absence of fever and significant electrolyte abnormalities, particularly sodium, calcium and phosphate along with hemoglobin level >10 gr/dL. Beyond all these, successful control of MC and Improvement In weakness was a must before attempting weaning. An Improvement In the strength of neck flexors (to greater than grade 4 according to the Medical Research Council Scale or able to hold head off the bed for at least 5 seconds) was considered critical In this respect.

In patients satisfying these weaning criteria, a spontaneous breathing trial (SBT) with continuous positive airway pressure (CPAP) was performed. Before this trial, patients were removed from mechanical ventilation for approximately 2 minutes, and tidal volume (Vt), respiratory rate (RR), minute volume (VE, calculated as RRxVt) and rapid-shallow breathing Index (RSBI, calculated as RR/Vt) were measured. Patients with Vt>5 cc/kg, RR <40 bpm, VE >10 L/minute and RSBI<105 were considered ready for SBT. For CPAP, minimal support was used (PEEP: 3-5 cmH2O, pressure support: no more than 5 cmH2O; FiO2 <40%; automatic tube compensation, at least 35%). During SBT, pulse oxygen saturation (SaO2), main-stream end-tidal carbon dioxide (etCO2), HR, BP and RR were monitored. The patient's appearance and presence of signs of tiredness, dyspnea, tachypnea, cyanosis and anxiety were noted. The SBT was stopped when there were significant changes In RR (decrease to <8 bpm or Increase to >40 bpm), BP (30 mmHg change In systolic BP or 10 mmHg In diastolic BP), HR (Increase of >20 bpm or HR>110 bpm) and appearance of cardiac arrhythmia (more frequent than 6 per minute). Other criteria for discontinuation were sustained decrease of SaO2 below 90%, decrease In GCS, occurrence of significant agitation, diaphoresis, progressive recruitment of accessory respiratory muscles and appearance of the thoracoabdominal paradox.

For subjects who passed the SBT, maximal Inspiration mouth pressure (MIP, also called PImax) and maximal expiratory mouth pressure (MEP, also called PEmax) were measured (MIcroRPM®, Micro Medical/ Care Fusion Ltd-UK), SpIroMed Ltd-Turkey). These measurements were repeated three to four times In the presence of variable results. For cough effectiveness, the white paper test was used. For this test, the size of the wet spot after a forceful cough onto a white paper towel held 1-2 cm from the tracheal tube was qualitatively classified as none, weak or strong. To assess the ability to control respiratory secretions, the modified Airway Care Score (ACS) was calculated (14, 15). Briefly, this system consists of five parameters (see Box 2), providing a total score of 0 to 15. The score was determined by consensus between one of the attending neurointensivists and the nurses examining the patient separately. Only subjects whose total ACS equal to or less than 7 underwent the extubation procedure. Afterwards, we proceed to a standardized cuff-leak test (13). Of note, ventilation mode was switched to volumecycled ventilation for this test. Inspiratory and expiratory V were measured for at least six breaths before and after cuff deflation and the difference between the medium three values was calculated and then averaged. The criterion for the absence of significant laryngeal edema was considered If the difference was less than 2 cc per body weight or less than 25%.

Patients who fulfilled these criteria were extubated using a standardized protocol. Briefly, two physicians (at least one as the attending neurointensivist) were present during the procedure. Prednisolone (usually 1 mg/kg IV) was administered before the leak test. Extubation was performed In high semi-Fowler position with the head In a neutral position. After explaining the process to the patient, an appropriate size Guedel (oropharyngeal) airway was placed to prevent tube biting. Before and after tube removal, 100% oxygen was applied (at least 5 minutes for each epoch). After suctioning the tube, subglottic catheters and the mouth for the last time, the tube was removed using an exchanger. Patients were monitored closely after removal, received nebulized salbutamol (200 μg) and Ipratropium bromide (500 μg) along with furosemid (0.5 mg/kg IV, If there was excess fluid on the last day). The exchanger was removed according to secretion status, at the latest 48 hours following extubation).

Extubation failure was defined as the reappearance of the need for ventilatory support within 72 hours of planned endotracheal tube removal. The criteria for reintubation after extubation were the presence peri-arrest status, serious air grasping, gagging or stridor, progressive decrease In cooperation and level of consciousness, significant hemodynamic Instability (systolic BP <90 mmHg despite vasopressor support), Intolerably high amount of secretions and jeopardized airway patency. In addition, In the presence of persistent hypoxemia (SaO2 <90% at least for 5 minutes), tachypnea (>40 bpm), accessory or superficial ventilation, throraco-abdominal paradox, hypoxemia (PaO2<50 mmHg), acidosis (arterial pH<7.3) or hypercapnia (PaCO2>60 mmHg), re-intubation was performed. An attempt for non-invasive MV (CPAP; with titration of PEEP and pressure support; via an oronasal mask) was performed In one of the patients with post-extubation ventilatory fa ilure. but re-intubation was performed 3 hours later, as this attempt was unsuccessful.

Statistical analysis

All values are displayed as mean ± standard deviation and percentage, as appropriate. Mann-Whitney U and Chi-square tests were used for exploratory analysis. For indices with p values less than 0.05, the area under the curve (AUC) of the receiver operator characteristic (ROC) curves and the 95% confidence intervals (95% CI) were calculated. The correlation between FRC and CT volumes was evaluated using the Spearman test. The SPSS® 15.0 and MedCalc® statistical package programs were used for the analyses. Due to the small sample size and primarily hypothesis-generating nature of the study, no adaptation of statistical significance level was considered, and p<0.05 was set as significant.

Results

We studied a total of 11 MC episodes in 10 patients (female/male: 8/2; mean age: 57±17 years; body mass index: 24.2±3.4). All patients underwent IMV for longer than 72 hours (mean: 11.8±5.2 days; range: 5-23 days). Extubation failure occurred in 55% of our MC patients who complied thoroughly with the standard weaning and extubation parameters indicating a sufficient extubation outcome. Individual patient data regarding myasthenia gravis and MC characteristics are presented in Tables 1 and 2, respectively.

The bedside FRC volumes (average and SD measured during the entire intubation period; latest 3 hours before SBT as absolute and normalized volumes ("cc" and "cc/kg")) were not significantly associated with extubation failure (Table 3). However, average FRC, last FRC and normalized FRC were non-significantly lower In subjects who were successfully extubated compared to those who required reintubation. No significant time trend was observed over the Intubation period (Figure 1).

There was no difference In total lung, effusion and atelectasis volumes measured on lung CT obtained during Intubation period among patients with (n=5) and without (n=4) failed extubation (Table 3). Of note, FRC and total as well as operant (defined as total volume-atelectasis volume) lung volume was well correlated (r=0.717; p=0.03 and r=0.733; p=0.025, respectively).

Most of the clinical, laboratory and pulmonary characteristics didn't differ significantly between patients with and without extubation failure, except for PIP, Pplato, CO2 gradient and airway care scores (Table 3). The AUC of ROC curves was 0.933 for PIP and 0.917 for Pplato (Figure 2). Of note, all the values of PIP and Pplato remained within normal limits regardless of the success or failure of extubation. The gradient of endtidal C02to arterial CO2 was high In five out of the six patients who could not been liberated from Intubation. The mean (Pa-et) CO2 was significantly higher In these patients (13.9±7 vs. 4.8±2.9 mmHg). The AUC of the ROC was 0.900 (Figure 2). The optimum threshold to predict success of extubation was 9.9 mmHg with a sensitivity of 22.7% and specificity of 48.0% specificity (lower limit of 95% CIs). Patients who tolerated extubation had significantly lower ACS compared to those who did not (2.8±0.8 vs. 5.3±1.0; p=0.004) (Table 4). The AUC of the ROC was 0.983 (Figure 2). The lower limit of the 95% CI of the sensitivity and specificity of the calculated cut-off value (4) was 36.1% and 48.0%, respectively.

Discussion

This study aimed to evaluate the value of bedside FRC measurement to predict success or failure of extubation In the MC recovery phase. Our results did not support our hypothesis that a low FRC volume relates to extubation failure In patients with MC. Considering the low enrollment rate and the need for more patients to achieve enough power to test this hypothesis, we stopped the study prematurely upon our first Interim analysis. Therefore, the value of the residual lung vol- umes determined either by lung CT or bedside FRC measurement in predicting success or failure of extubation remains to be confirmed in future studies. However, this study underscores the fact that serial bedside FRC measurement is safe, feasible and easily attainable in this population. Its correlation to lung CT was satisfactory despite the low number of subjects studied.

This prospective pilot study supports the concept that usual weaning criteria may not be accurate in predicting reintubation after planned extubation (4). Indeed, extubation failure could not be predicted based on most of the individual weaning parameters such as RSBI, Vt, VE, PF ratio, P100, and respiratory rate in our patients. Certainly, the pathophysiology underlying success in weaning and extubation are significantly different (4). In patients recovering from MC and passing the SBT successfully, it is crucial to pay special attention to usual extubation predictors such as the ability to protect upper airways, adequacy of cough strength, extent of respiratory secretions and the degree of consciousness. However, all of our patients who required reintubation had passed most of these criteria as well. Therefore, extubation still remains problematic for a significant proportion of MC patients who totally comply with the widely-used criteria. Our univariate analyses suggest the role of higher PIP, Pplato and (Pa-et) CO2 gradient and a lower airway care score in predicting failed extubation.

While Pplato reflects elastic recoil force (elastance) of the lungs and chest wall, PIP reflects both elastance and airway resistance. Therefore, when both PIP and Pplato are increased, the problem is decreased compliance, frequently due to pneumothorax, atelectasis, edema, pneumonia, abdominal distention, auto-PEEP or fighting against the ventilator. When PIP is increased but Pplato stays within the normal limits, the problem is usually airway obstruction due to secretions, aspiration, tube problems or bronchospasm. In our series, patients unable to be liberated from the endotracheal tube showed higher PIP and Pplato values compared to those who remained extubated. Although all the values were below the permitted levels (30 and 40 cmH2O for Pplato and PIP, respectively), this finding can still Indicate a potential role of abnormalities at the pulmonary level In the extubation process.

An arterial to end-tidal C02gradient exceeding 3 (or 5) mmHg Indicates Increased anatomic and/or physiological dead space, as well as low cardiac output due to heart failure, pulmonary embolism or overdistention. In complicated weaning, an Increase of etCO2 Indicates an Increase In the work of breathing, which may be a signature of weaning failure. In contrast, a decrease In etCO2 and a corresponding Increase In the gradient can signify respiratory muscle weakness, which Is also a marker of weaning failure. Our study Indicated that extubation failure was also associated with an Increase In the CO2 gradient due to a decrease In etCO2. This was probably due to residual neuromuscular weakness. Because of simplicity of this parameter, we think that future weaning and extubation studies should consider this parameter, which actually has not previously been studied In neuromuscular respiratory failure.

The total points on the airway care score was the best predictor of extubation In this small group of patients recovering from MC. This score consists of cough strength to stimulation by a suction catheter, sputum quantity, character and viscosity along with suctioning frequency correlated with the amount of secretions (15). In myasthenic patients, the most Important cause of Increased bronchial secretions Is pneumonia. However, the most prevalent cause Is perhaps over dosage of parasympathomimetic reversible cholinesterase Inhibitors such as pyridostigmine used In these patients. A meticulous titration against atropine oral drop and an Ipratropium Inhaler may be Important In this respect, In addition to Infection protection and management. Aggressive airway suction and chest physiotherapy are also valuable strategies.

In addition to an excess of secretions, cough capacity and airway protection ability are critical factors for extubation success. Bedside tests such as an evaluation of the gag reflex, evaluation of cough strength by MEP and MIP and the paper test have been reported to be useful. MEP Is a measure of cough power, which Is based on the flow generated by expiratory muscles to allow airway clearance. Some studies have Indicated the superiority of MEP over other parameters such as vital capacity. However, we found that the measurement of MEP and MIP Is quite complicated In patients with an endotracheal tube In place.

Conclusion

The predictive value of widely-used criteria may be not more than moderate for assessing extubation In MC. Secretions and perhaps cough status are the most Important parameters. Capacity to control airway patency and aspiration are the second most Important. Our study did not support but still recognizes the value of lung volumes and reserves In this process.

Conflict of Interest

This study was funded by the Hacettepe University Research Fund (Project no: 08A101011)

References

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