Tapered-cuff Endotracheal Tube Does Not Prevent Early Postoperative Pneumonia Compared with Spherical-cuff Endotracheal Tube after Major Vascular Surgery: A Randomized Controlled Trial

POSTOPERATIVE pneumonia is a nosocomial infection that occurs after surgery, at least 48 h after hospital admission in the absence of previous signs of incubation. Preexisting comorbidities (such as advanced age, diabetes, and chronic obstructive pulmonary disease), surgical incision (e.g., thoracotomy or sternotomy), intraoperative bleeding requiring massive blood transfusion, and long duration of surgery expose patients undergoing major vascular surgery to a high risk of postoperative pneumonia. The postoperative pneumonia rate after such surgery is around 20%, with a sharp increase after 48 h of mechanical ventilation that can reach 40% after major thoracic surgery.¹  Postoperative pneumonia is responsible for a significant economic burden¹  and remains a leading cause of morbidity and mortality, with associated mortality rates ranging between 15 and 45%.^1–3 

Although postoperative pneumonia often occurs within the first few days after starting mechanical ventilation, it shares common underlying mechanisms with ventilator-associated pneumonia (VAP). Colonization of oropharyngeal secretions with oral or gastric pathogens is commonly viewed as the first step toward postoperative pneumonia and/or VAP. Gravity then pulls them downward, converging toward subglottic area and then to the tracheobronchial tree. Despite implementation of the preventive bundle to thwart postoperative pneumonia and/or VAP, subglottic secretions can still leak through the microchanneled folds that rapidly spread on the surface of any high-volume, low-pressure endotracheal tube’s cuff.^1,4  Subsequent and repetitive microaspiration of subglottic secretions, which carry a high bacterial burden into the distal airways, plays a pivotal role in postoperative pneumonia pathogenesis.¹ 

Improving cuff design by changing the material or modifying the shape is among the strategies used to enhance its sealing properties. Bench studies showed promising results in terms of reducing air or liquid leakage across the cuff when using a new tapered-shaped cuff compared with the standard-shaped (spherical or cylindrical) cuff.^5–7  This new design was based on the concept that a conical shape would provide a better fit between the trachea and the cuff. Currently available data are discrepant concerning the tapered-cuff’s efficiency at preventing microaspirations,^8–10  VAP,¹¹  and bacterial colonization of the tracheal tree¹²  in critically ill patients. A recent, two-period, observational study did not show any VAP rate differences before and after implementing the use of tapered-cuff endotracheal tubes.¹¹  However, in that study, adherence to the VAP-prevention bundle was significantly lower during the tapered-cuff period, precluding fair comparison. On the other hand, tapered-cuff endotracheal tubes have never been evaluated in postoperative pneumonia prevention.

We designed this prospective randomized controlled study to assess the effect of tapered-cuff endotracheal tubes on the postoperative pneumonia rate and microaspiration frequency in major vascular surgery patients.

This prospective, randomized controlled, single-blind study was conducted in our 26-bed multidisciplinary intensive care unit (ICU) during a 48-month period. The study was approved by the Institutional Ethics Committee Île-de-France VI (Institutional Review Board of La Pitié-Salpêtrière Hospital, Paris, France; #ID-RCB-2011-A01038-33). Because our protocol did not modify usual patient care, and the two types of endotracheal tubes were also routinely used in the operating room, the institutional review board waived signed consent. Patients and/or their relatives received written information. The study was registered with ClinicalTrials.gov (NCT01457248).

The inclusion criteria were patients older than 18 yr; who were scheduled to undergo major thoracic, thoracoabdominal, or abdominal aorta surgery without pulmonary exclusion requiring intubation with a double-lumen endotracheal tube; and justifying systematic admission to the multidisciplinary ICU for postoperative care. Patients admitted to the ICU with prior tracheostomy, already enrolled in another trial, or who had had pneumonia within 1 month before the planned surgery were excluded.

A computer-generated randomization list gave an allocation table in permuted blocks (fixed block size, 10; allocation ratio, 1:1). Treatment allocation was concealed, using sequentially numbered opaque sealed envelopes. Patients were screened according to the surgery schedule established 1 week before the intervention. Investigators recruited patients satisfying inclusion criteria and provided information on the study whenever possible before randomization. The anesthesiologist took the next assignment envelope (standard cuff or tapered cuff) in the operating room before anesthesia. Standard-cuff patients were intubated with High Contour Brandt endotracheal tube incorporating a polyvinyl chloride (PVC) spherical-shaped cuff (Mallinckrodt Medical, USA). Tapered-cuff patients were intubated with TaperGuard (Covidien, Ireland) (fig. 1). The endotracheal tube size and the insertion technique were chosen according to professional guidelines. The Cormack–Lehane score and difficult airway-management rate were recorded. Endotracheal tube cuff-pressure setup and management are described in Methods (Supplemental Digital Content 1, https://links.lww.com/ALN/B258). Briefly, the cuff was inflated to 25 cm H₂O and manually checked with a manometer every 6 h. The different external appearances of the two tracheal tubes rendered blinding of the randomization arm to physicians and nurses impossible. Antibiotic prophylaxis (IV cefamandole; initial dose: 1.5 g, and 750 mg every 2 h) was administered intraoperatively and stopped at the end of surgery. After surgery, all patients were directly admitted to the ICU for postoperative care. They were screened daily for clinical suspicion of postoperative pneumonia for 5 days postextubation or until day 28 if the patient could not be weaned off mechanical ventilation. Tracheal aspirates were sampled within the first hour after the patient’s admission (day 1) and 24 h later (day 2) for quantitative pepsin and α-amylase determinations. Cuff pressure was continuously recorded during the 5 h after ICU admission.

The primary endpoint of the study was the frequency of first postoperative pneumonia episodes. The secondary endpoints were as follows: time from intubation to postoperative pneumonia diagnosis; rate of second pneumonia episodes, defined as pneumonia diagnosed after 8 days of antimicrobial treatment for the first pneumonia episode; microaspiration frequency, assessed by tracheal aspirate pepsin and α-amylase concentrations; cuff-pressure variations; lengths of mechanical ventilation and ICU stay, and 28-day mortality.

Pneumonia diagnosed between intubation and the 5th day post extubation was considered the first postoperative pneumonia episode. Postoperative pneumonia was suspected based on Johanson criteria¹³ : new or persistent infiltrates on chest radiography and/or new bedside lung-ultrasound patterns highly evocative of lung infection¹⁴  (see Methods, Supplemental Digital Content 1, https://links.lww.com/ALN/B258), associated with two of the three following clinical features: temperature 38.4°C or greater or less than 36.5°C, leukocyte count greater than 11 × 10³/ml, and/or purulent bronchial secretions. For mechanically ventilated patients, the postoperative pneumonia diagnosis was confirmed when Johanson criteria were associated with a significant concentration of bacteria isolated in lower respiratory tract specimens obtained by fiber-optic bronchoscopy with nonprotected bronchoalveolar lavage or protected mini-bronchoalveolar lavage.¹⁵  A positive sample contained 10⁴ or greater colony-forming units per milliliter for nonprotected bronchoalveolar lavage¹⁶  and 10³ or greater colony-forming units per milliliter for protected mini-bronchoalveolar lavage.¹⁷  For spontaneously breathing patients meeting the Johanson criteria whose lower respiratory tract secretions could not be sampled or ventilated patients meeting those criteria whose lower respiratory tract specimens were negative, a postoperative pneumonia diagnosis was considered possible.^18,19  Two independent board-certified investigators (attending physicians), blinded to study-arm assignment, made the final pneumonia diagnosis, including the interpretation of chest radiographs and/or lung ultrasounds.

On day 1, immediately after surgery, and on mechanical ventilation day 2, pepsin and α-amylase in tracheal aspirates were measured quantitatively with enzyme-linked immunosorbent assays (Biochemistry and Molecular Biology Laboratory, CHRU, Lille, France). Processing method of tracheal aspirate samples and pepsin and α-amylase quantification techniques were described previously (see Methods, Supplemental Digital Content 1, https://links.lww.com/ALN/B258).²⁰  Concentrations of pepsin greater than 200 ng/ml²¹  and α-amylase greater than 1,685 μg/l defined abundant microaspiration.^20,22,23  Biochemists who measured pepsin concentrations were blinded to study-group assignment.

During the first 5 h after ICU admission, maximum (P_max), minimum (P_min), and mean (P_mean) cuff pressures were digitally recorded continuously at 100 Hz, with Physiotrace software (Centre d’Investigation Clinique-Innovation Technologique, Centre Hospitalo-Universitaire, France). Cuff pressures were defined as normal (20 to 30 cm H₂O), underinflated (less than 20 cm H₂O), or overinflated (greater than 30 cm H₂O). P_max, P_min, and P_mean cuff pressures and the time in each pressure zone were recorded. The coefficient of cuff-pressure variation was calculated as follows: [(P_max − P_mean) + (P_mean − P_min)]/2.⁹ 

In the ICU, VAP-prevention strategies were routinely applied to both groups of patients. The measures included the following: cuff pressure measured every 6 h using a manual manometer (Ambu Cuff Pressure Gauge; Ambu A/S, Denmark) and maintained between 20 and 30 cm H₂O; semirecumbent body position maintained between 30° and 45°; enteral nutrition with quantification of residual gastric volume every 6 h; stress-ulcer prevention with a proton-pump inhibitor; and oral decontamination with hexetidine every 6 h. All patients were mechanically ventilated with tidal volume of 6 ml/kg of ideal body weight.²⁴  The end-expiratory–pressure level was set by the patient’s treating physician.

The primary outcome analysis evaluated the first postoperative pneumonia episode frequencies for “tapered-cuff” patients versus “standard-cuff” patients. The postoperative pneumonia rate after major vascular surgery in our ICU was 48% for patients intubated with standard-cuff endotracheal tubes in 2010. We estimated that, with a 5% risk and 80% statistical power, 112 patients (56 in each group) would be needed to detect a 50% reduction of pneumonia frequency in the tapered-cuff group compared with the standard-cuff group, based on previously published data.^11,25–30  The primary endpoint analysis was performed on the per-protocol population, defined as randomized patients who were admitted to the ICU immediately after surgery. Patients who were randomized before surgery but transferred to another ward or another ICU outside the study center on day 1 after the intervention were considered lost-to-follow-up early; they were excluded from the analysis.

Categorical variables are expressed as numbers (%) and continuous variables as medians (25 to 75% interquartile range). A two-tailed hypothesis was tested. Differences between standard-cuff and tapered-cuff groups for patients’ characteristics, perioperative factors, primary and secondary outcome measures, inner cuff pressures, and pepsin and α-amylase concentrations were compared using chi-square, Fisher exact, or Mann–Whitney rank sum test, as appropriate. Relative risk and its 95% CI were calculated for the primary outcome. The cumulative rates of patients remaining postoperative pneumonia-free from enrollment to day 28 were analyzed with the Kaplan–Meier method and compared between groups using a log-rank test. Statistical analyses were computed with SPSS v13.0 (SPSS, USA) and SigmaStat v3.5 (SystatS, USA). A P value of less than 0.05 defined significance.

Among 123 patients undergoing planned major vascular surgery screened for inclusion from October 2011 to September 2013, 114 patients were randomized: 58 assigned to the standard-cuff group and 56 allocated to the tapered-cuff group. Five patients were secondarily excluded from the study within 1 day after surgery (fig. 2), leaving 57 and 52 patients to be analyzed in the standard- and tapered-cuff groups, respectively. Their clinical characteristics at ICU admission are reported in table 1. Other than positive end-expiratory pressure (PEEP), which was higher for the tapered-cuff group, intra- and postoperative risk factors for postoperative pneumonia were comparable for the two groups (table 2).

As shown in table 3, first postoperative pneumonia frequencies did not differ between standard- and tapered-cuff groups (44 vs. 42%, P = 0.87, relative risk = 0.97; 95% CI, 0.70 to 1.35). Sixteen standard-cuff patients and 15 tapered-cuff patients had microbiologically confirmed postoperative pneumonia (table 4). Nine standard-cuff patients and seven tapered-cuff patients had possible postoperative pneumonia. The cumulative rate of patients remaining postoperative pneumonia-free from enrollment to day 28 did not differ between groups (P = 0.71; fig. 3). As shown in tables 3 and 4, clinical and bacterial postoperative pneumonia characteristics and outcome data were comparable for the two groups.

Tracheal aspirate pepsin levels exceeded 200 ng/ml in 23% of standard-cuff patients and in 20% of tapered-cuff patients (P = 0.51) at ICU admission (day 1) (fig. 4). On day 2, the percentage of patients with pepsin concentration greater than 200 ng/ml remained unchanged for the tapered-cuff group (19%), while it increased, albeit not significantly, to 35% for the standard-cuff group (P = 0.11). Using the previously validated cutoff of 1,685 μg/l, tracheal aspirate α-amylase concentrations showed that 37 and 52% of the patients had significant oropharyngeal microaspirations on days 1 and 2, respectively. No significant between-group differences were found for microaspiration rates and absolute α-amylase values on postoperative days 1 and 2 (fig. 5).

The tapered-cuff group’s P_max was significantly higher and P_min significantly lower than those of the standard-cuff group (table 5). Comparing the tapered-cuff group to the standard-cuff group, respectively, the coefficient of cuff-pressure variation and the time with cuff overinflation were significantly higher, the time with cuff pressure within the normal range was significantly shorter, and the time with cuff underinflation was longer, but the latter difference did not reach statistical significance (P = 0.06). Illustrative cuff-pressure recordings are shown in figure 6.

The results of this study showed that using tapered-cuff endotracheal tubes in major vascular surgery patients did not prevent the first postoperative pneumonia epidode, failed to prevent intraoperative gastric or oropharyngeal microaspiration, generated higher variability of cuff inner pressure, increased the time with cuff overinflation, and decreased the time with normal cuff pressure.

The rationale for designing a tapered-shaped cuff was based on the assumption that a continuum of minimum-to-maximum diameter sections might better fit the tracheal walls than a standard cuff with single fixed diameter. Improving the fit between trachea and cuff walls would expand the surface area with few or no folds, thereby reducing the number of microchannels toward distal airspace, which might ultimately result in improved tracheal sealing.

Bench-study findings comparing a tapered cuff to either spherical- or cylindrical-shaped cuffs highlighted better sealing properties in terms of liquid and gas leakages.^6,7  However, obvious methodological limitations of such in vitro studies preclude any generalization of their observations to clinical settings. In addition, when polyurethane tapered cuffs were tested in similar settings, the tapered cuff’s superiority was not confirmed.^6,7  Perioperative sealing properties of tapered cuffs were assessed in a clinical study conducted on patients in a prone position for lumbar surgery. D’Haese et al.⁸  used bronchoscopic examination to assess colored-dye leakage across the cuff. Although their results suggested significantly less tracheal aspiration of the dye with tapered-cuff endotracheal tubes, some methodological limitations should be noted. Prone positioning can increase the risk of gastric content aspiration and impact the determinants of tracheal sealing, and evaluations concerned short 10- to 120-min periods. Aspiration was diagnosed based on bronchoscopic detection of liquid-dye–volume leakage, as its viscosity is much lower than that of oropharyngeal secretions.

The first postoperative pneumonia episode after major aorta surgery is thought to be most closely related to intraoperative risk factors for microaspiration, potentially prevented by improving perioperative tracheal sealing. In contrast, the second episode is mostly associated with prolonged invasive mechanical ventilation and other factors leading to VAP and/or hospital-acquired pneumonia, which are more independent of intraoperative events. For this study, we considered the first postoperative pneumonia episode, diagnosed between intubation and day-5 postextubation, to be mainly attributable to intraoperative microaspiration events. In contrast, because pneumonia developing after day-5 postextubation could reflect other factors driving late hospital-acquired pneumonia rather than endotracheal tube and microaspiration events, its episodes were not considered herein. All patients remaining pneumonia-free 5 days postextubation were discharged from the ICU but were followed until day 28; none was readmitted to the ICU for pneumonia.

This randomized, controlled trial investigating the potential advantage of PVC tapered-cuff endotracheal tubes to prevent the first postoperative pneumonia episode was conducted on patients undergoing major vascular surgery because this population carries a high risk of postoperative lung infection. Although initially subjected to short-term ventilation for surgery,³¹  these patients were exposed intraoperatively to numerous risk factors for microaspiration (e.g., surgery duration, body position, and transesophageal echocardiography) that might have been prevented by intraoperative use of a tapered-cuff endotracheal tube.¹  Moreover, patient-related factors (age, chronic obstructive pulmonary disease, diabetes, and immunodeficiency) increase the risk of developing postoperative pneumonia. As expected, around 40% of patients developed early postoperative pneumonia. Similar postoperative pneumonia rates, ranging from 30 to 48%, were reported after cardiothoracic surgery.^32–37  Among patients meeting Johanson criteria, 66% had microbiologically confirmed pneumonia and 34% had possible pneumonia. The negative respiratory samples of 9 of the 16 patients with possible pneumonia could reflect antibiotic use (intraoperative prophylaxis or aorta-prosthesis–related sepsis) before specimen collection. However, intraoperative antibiotic use did not differ significantly between the two study groups.

Unfortunately, our results showed that tapered-cuff endotracheal tubes did not prevent early postoperative pneumonia. Similarly, two recent prospective studies showed that the use of tapered-cuff endotracheal tubes did not lower the VAP rate for critically ill patients intubated for various causes of respiratory failure.^11,12  The inability to prevent VAP likely reflects the inability to prevent intraoperative microaspiration during major vascular surgery. Last, tapered-cuff endotracheal tubes cannot reduce the risk factors resulting from comorbidities, elevated disease severity scores, and massive blood transfusion, all frequently observed in patients undergoing major vascular surgery.

Our microaspiration results agree with those of two randomized controlled trials that enrolled medical ICU patients and showed that tracheal aspirate pepsin levels did not differ between tapered- and cylindrical-cuff groups.^9,10  However, those studies used polyurethane cuffs, which could explain the lack of benefit of cuff shape on sealing properties, as reported in in vitro studies.^6,7  To the best of our knowledge, tracheal sealing properties of PVC tapered cuffs have never been assessed through tracheal pepsin or α-amylase level measurements. Because pepsin is a gastric marker, monitoring its tracheal aspirate level might have underestimated the true oropharyngeal microaspiration frequency. Therefore, we also measured tracheal α-amylase, an oropharyngeal marker, which confirmed that overall (oropharyngeal and gastric) microaspiration events did not differ between standard- and tapered-cuff groups.

Another factor that might explain the failure to prevent postoperative pneumonia is the significantly higher coefficient of cuff-pressure variation with the tapered-cuff, compared with the standard cuff (table 5). As shown in a bench study,³⁸  tapered cuffs had the lowest tracheal wall contact area compared with other-shaped cuffs. This small contact area might lead to cuff slippage and, hence, to cuff-pressure fluctuation over time. As a consequence, the times with cuff overinflation and underinflation were longer for the tapered-cuff group. These effects are potentially detrimental: cuff underinflation–induced microaspiration might enhance the risk of postoperative pneum onia, whereas cuff overinflation might produce trachea-wall ischemia.³⁹  Although no adverse effects (e.g., postextubation stridor or tracheal stenosis) were observed herein, our findings suggest that close monitoring and continuous cuff-pressure control would be required if tapered-cuff endotracheal tubes were to be used.

The current study has some limitations. First, the cuff material might impact its tracheal sealing properties. Although two bench studies found that polyurethane tapered cuffs had no benefits for microaspiration reduction, their preventive role in postoperative pneumonia remains to be investigated further. Second, in many previously published studies, the control group was composed of patients intubated with cylindrical-cuff endotracheal tubes.^9,11,12  Our control patients were intubated with standard (spherical)-cuff endotracheal tubes. Given that PVC spherical-cuff endotracheal tubes are used worldwide, with proven good performances,⁴⁰  have been compared in multiple clinical trials,^40–44  and are routinely used in our surgical center as standard practice for patients undergoing major vascular surgery, we considered that such control group management would not introduce bias into our trial. Third, although statistically significant (5 vs. 5.6 cm H₂O, P = 0.03), the mean PEEP level difference observed between groups was much lower than that demonstrated to affect tracheal sealing.^7,45  For this reason, we think that such a low PEEP level difference (0.6 cm H₂O) did not induce major bias into our trial. Last, the lack of continuous cuff-pressure control might have blunted the potential benefit of tapered-cuff endotracheal tubes in terms of sealing properties. Indeed, it was shown that continuous cuff- pressure control using a mechanical device reduced cuff-pressure fluctuation and the time in underinflation for a series of critically ill patients intubated with tapered- or cylindrical-cuff endotracheal tubes.¹⁰  Although available data on the benefits of continuous cuff-pressure control for microaspiration events and VAP prevention are contradictory,^10,21,46,47  two monocenter randomized controlled trials have reported that continuous control of cuff pressure either mechanically or electronically may prevent VAP.^21,47  Therefore, it cannot be excluded that the better sealing properties of the tapered-cuff endotracheal tube may have been offset by intermittent cuff-pressure control. The lack of randomized controlled multicenter trial explains why, to date, no recommendations for routine use of continuous cuff-pressure control as a VAP-preventive measure have been issued.⁴⁸  Some caveats had been raised concerning the use of certain automated cuff-pressure controllers, leading to worse tracheal sealing and potentially cause trachea-wall injury.⁴⁹  Additional studies are required to assess the impact of continuous cuff-pressure control on efficiency of tapered- and spherical-cuff endotracheal tubes to prevent gastric aspiration and postoperative pneumonia.

In conclusion, our results did not show that PVC tapered-cuff endotracheal tubes using intermittent manometer control of cuff pressure was superior to standard-cuff endotracheal tubes to prevent postoperative pneumonia in major vascular surgery patients. The higher cuff-pressure variability and higher percentages of time with tapered-cuff overinflation and underinflation represent a potential caveat that deserves further investigation. The impact of continuous cuff-pressure regulation on the ability of tapered cuffs to prevent microaspiration, postoperative pneumonia, and/or VAP needs to be evaluated.

The authors thank Patrice Maboudou, M.D. (Department of Biochemistry and Molecular Biology of the Centre de Biologie Pathologie, Centre Hospitalo-Universitaire de Lille, Lille, France), who did the amylase level measurements in tracheal aspirates.

Dr. Dexheimer was supported by grants from the doctoral fellowship program of the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Office for the Advancement of Higher Education), Brazilian Ministry of Education, Porto Alegre, Brasil (grant no. BE 6869/13-1). Dr. Wang, a research fellow, was supported by a grant from Peking Union Medical College Hospital, Beijing, China.

The authors declare no competing interests.

Full protocol available from Dr. Monsel: antoine.monsel@aphp.fr. Raw data available from Dr. Monsel: antoine.monsel@aphp.fr.

Members of the Tapered Endotracheal Tube to prevent Respiratory Infections (TETRIS) Study Group:

The TETRIS study group members are authors of this article and the following investigators: Liliane Bodin, M.D., Romain Deransy, M.D., M.Sc., Pierre Garçon, M.D., Hatem Douiri, M.D., Ismael Khalifa, M.D., Antoine Pons, M.D. (Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care, La Pitié–Salpêtrière Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France); Wen-Jie Gu, Ph.D. (Clinical Research Department, La Pitié–Salpêtrière Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France); Fabien Koskas, M.D., Ph.D., Julien Gaudric, M.D. (Department of Vascular Surgery, La Pitié-Salpêtrière Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France).