This article is accompanied the following Invited Commentary:
De Hert S, De Baerdemaker L. Randomised controlled trials. Are we looking at treatment effects or absence of good clinical practice in control groups? Eur J Anaesthesiol 2014; 31:450–451.
Pulmonary endarterectomy (PEA) is an established surgical method for the treatment of chronic thromboembolic pulmonary hypertension. The procedure involves the removal of fibrous obstructive tissue from the pulmonary arteries and requires several periods of deep hypothermic circulatory arrest (DHCA). Recently published data from the international registry showed that PEA is associated with relatively high morbidity and that perioperative complications occurred in more than 49% of patients, of whom nearly 20% were reported as having infection (most commonly ventilator-associated pneumonia, VAP).1
It is known that both tracheal tube cuff overinflation and underinflation during mechanical ventilation may contribute to tracheal pressure injury or allow leaking of secretions beyond the cuff and silent aspiration, predisposing to VAP.2,3 The risk of pneumonia is at its highest during the first few days of prolonged mechanical ventilation.4 Several authors recommend that tracheal tube cuff pressure should not exceed 30 cmH2O during surgery to prevent tracheal injury.3,5 In contrast, other authors recommend keeping pressure in the cuff above 20 cmH2O to reduce the risk of pneumonia.6 Apart from cuff pressure, the outer diameter of the cuff, its shape and length, and the material it is made from may also affect its capacity to seal the trachea.7,8
One of the key determinants of tracheal tube cuff pressure during surgery is temperature. This is particularly important during cardiac surgery, in which body temperature is altered therapeutically during cardiopulmonary bypass (CPB).9,10 Although the effect of active management of the tracheal tube cuff in the operating theatre and the ICU has been investigated previously,11–13 this has not been studied when DHCA, routine in PEA surgery, is used.14 Indeed, pressure control of the tracheal tube cuff is not discussed in current DHCA protocols.15,16
We therefore hypothesised that active management of the cuff of the tracheal tube during DHCA would reduce silent subglottic aspiration. We also determined to study its effect on postoperative mechanical ventilation and positive tracheal microbiology cultures.
Materials and methods
We undertook a single-centre, randomised, controlled study of the effect of active management of tracheal tube cuff pressure, after approval from our local ethics committee (Ethics Committee of the General University Hospital, Prague chaired by Josef Sedivy, MD, PhD, Na Bojišti 1, 12808 Prague 2, protocol number 1253/08 S-IV, approved on 21 August 2008) and with informed consent from the patients. From September 2008 to November 2009, consecutive patients undergoing PEA with CPB and DHCA who gave written informed consent were recruited and randomised to active cuff management (study group) or cuff pressure monitoring without adjusting cuff volume or pressure (control group). Patients with a history of oesophageal disease or requiring combined PEA and other surgery were excluded (Fig. 1).
On the day of surgery, patients were premedicated with oral alprazolam 0.25 mg (Neurol, Zentiva, Slovakia) and transferred to the operating theatre. Total intravenous anaesthesia was administered, consisting of sufentanil (Sufentanil Torrex; Chiesi CZ, Prague, The Czech Republic), midazolam (Dormicum; Roche, Prague, The Czech Republic), the muscle relaxant rocuronium (Esmeron; Organon Ltd., Swords, Ireland) and propofol (Propofol; Fresenius Kabi, Bad Homburg, Deutschland). We did not use nitrous oxide or volatile anaesthetic agents. In all patients, the trachea was intubated with a size 7.5 mm tube in women and 8.5 mm in men (Kendall Curity, Tyco Healthcare, Mansfield, USA). This tube has a low-pressure, high-volume cylindrical cuff and a Murphy's eye. No lubricant was applied to the tracheal tube. The cuff was inflated with room air and pressure adjusted to 25 cmH2O using a Portex Cuff Inflator/Pressure Gauge (Smiths Medical International Ltd, Hythe, Kent, UK). Mechanical ventilation of the lungs was carried out using the anaesthetic machine (Datex Ohmeda Aespire; GE Company, Madison, Wisconsin, U.S.A.) in pressure control mode with positive end-expiratory pressure (PEEP) of 8 cmH2O and tidal volume up to 6 ml kg−1 to achieve normocapnia (end-tidal CO2 partial pressure 4 to 4.7 kPa). Immediately after tracheal intubation, 1 ml of methylene blue dye (Patentblau V; Guerbert, Roisse, France) diluted in 2 ml of physiological saline was injected into the hypopharynx from a syringe under laryngoscopic control. During surgery, body temperature was measured in the hypopharynx, the rectum and the bladder. Routine antibiotic prophylaxis was administered 1 h before skin incision and continued for 48 h.
After sternotomy and institution of CPB, mechanical ventilation of the lungs was discontinued and the patient was actively cooled to 16°C to 18°C. DHCA was used twice, for the endarterectomy of each pulmonary artery, with reperfusion in between. Our DHCA management included bispectral analysis monitoring (BIS View Monitoring System; Aspect Medical Systems, Inc, Norwood, Massachusetts, U.S.A.), packing of the head in ice, thiopental 20 mg kg−1 (Thiopental, VUAB, Roztoky, The Czech Republic), intravenous methylprednisolone 30 mg kg−1 (Solu-Medrol, Pfizer, Puurs, Belgium) given before arrest and active maintenance of normoglycaemia using a sliding insulin scale.
The pressure of the tracheal tube cuff was checked when the temperature measured in the hypopharynx was 36°C, 32°C, 28°C, 24°C, 20°C and finally at minimum temperature, just before DHCA. Patients were randomised using an envelope technique to active cuff management (study group) or cuff pressure monitoring alone (control group). In the study group, the cuff was reinflated whenever pressure dropped below 20 cmH2O, up to its starting value of 25 cmH2O. During rewarming, cuff pressure was also checked at the same temperature points, and the cuff was deflated if pressure exceeded 30 cmH2O. In the control group, cuff pressure was checked but not altered and no air was added to or removed from the cuff. Immediately before weaning from CPB, fibreoptic bronchoscopy was performed by an anaesthetist who was blinded to the allocation group. If blue dye was seen in the trachea below the tracheal cuff, silent aspiration was deemed to have occurred.
We expected 50% of patients to have leakage of blue dye (mean 50%, SD 33%) past the cuff of the tube, therefore we hoped for a reduction to 25% with active cuff pressure management, in other words a reduction of 50%. Assuming α 0.05 and β 0.80, we needed 12 patients per group. Data were analysed using the Mann–Whitney U-test or Fisher's exact test as appropriate, and S and SPSS 13.0 (SPSS, Chicago, Illlinois, USA). The data were tested for normal distribution using the Shapiro–Wilk and the Kolmogorov–Smirnov tests. All values are expressed as mean ± SD and median (25th to 75th percentiles) for normal and nonnormal variables, respectively.
The study and control groups were similar except that the former were younger (51.2 ± 11.6 vs. 63.2 ± 9 years, P = 0.028). CPB, DHCA and lowest temperature achieved were also similar (Table 1). Patients in the control group were mechanically ventilated for longer postoperatively [50, interquartile range (IQR) 28.5 to 93.5 vs. 32, IQR 19.5 to 39.8 h] (P = 0.038). Patients in the control group had significantly lower intracuff pressure during cooling and during rewarming at all timepoints (Fig. 2 and Table 2). In 10 of the 12 control group patients, the intracuff pressure decreased below 20 cmH2O during cooling, and in seven of the 12 study group patients, the intracuff pressure exceeded 30 cmH2O during rewarming. The primary endpoint of the study was reached, because we showed that that silent aspiration (blue dye in the trachea) was less common in the study group (0/12 vs. 8/12 patients, P = 0.001). Two patients in the study group required mechanical ventilation for more than 48 h, and there were no positive microbiology cultures from tracheal aspirate in these two patients. In the control group, six patients required mechanical ventilation for more than 48 h, and, of these, four had positive microbiology cultures (Escherichia coli in two patients, Staphylococcus haemolyticus and Peptosptreptococcus anaerobius) from tracheal aspirates (P = 0.01) (Table 3). There were no deaths or gross neurological dysfunction in either group.
We have shown that regular adjustment of tracheal tube cuff pressure during cardiovascular surgery and DHCA is associated with a decreased incidence of silent aspiration. DHCA may be an important cause of morphological change in tracheal cuff integrity, as body temperature falls during the cooling phase, thereby reducing cuff pressure, which may result in leak of oropharyngeal secretions into the trachea. The opposite is likely during rewarming, and increased cuff pressure during this phase of the operation may predispose to cuff pressure injury to the trachea. Tracheal cuff pressure during cardiac surgery can be affected by multiple factors. These include sternotomy and pericardiotomy itself, which may reduce pleural pressure on the tracheal wall. Alterations in muscle tone in the neck muscles surrounding the trachea can also partially explain cuff pressure changes.10 It has also been shown that tracheal cuff pressure changes may follow mean arterial pressure and that the nadir may occur during hypothermia and CPB, which may actually protect the trachea from hypotensive ischaemic injury.10 The mechanism by which hypothermia during CPB decreases tracheal tube cuff pressure is poorly understood, but may be related to vasoconstriction during hypothermia and shrinkage of the microvasculature of the tracheal mucosa, which results in widening of the tracheal diameter. Temperature change may also have a physical effect on the polyvinylchloride plastic used for tube manufacture.9 Finally, Charles’ law explaining the relationship between gas volume and temperature is also important. It states that the volume of a given amount of gas is directly proportional to the temperature provided that the amount of gas and the pressure remain fixed; that is, the volume of the gas increases or decreases by the same factor as its temperature. All of these effects are more likely as a result of the profound changes during DHCA, and we have shown that their effects are relevant with regard to aspiration of pharyngeal contents during anaesthesia and surgery.
Limitations of our study include the small group sizes and the fact that patients in the study group were younger in age. This may have had an impact on the reduced postoperative duration of mechanical ventilation and incidence of positive tracheal cultures seen in this group, but does not explain the greatly reduced incidence of passive aspiration demonstrated by tracheal staining with dye in the study group. The study was not powered for postoperative pneumonia, because its cause is multifactorial and diagnosis is challenging. According to published criteria,17 VAP is defined as the presence of new infiltrate on chest radiograph along with two of the three following conditions: core temperature more than 38.3°C, leukocytes more than 10 × 109 l−1 and purulent tracheal secretions. However, many if not all patients following PEA demonstrate both leucocytosis and new infiltrates on postoperative chest radiograph, and fever is also not uncommon. Therefore, we usually make a final diagnosis of pneumonia by examining trends in daily procalcitonin levels, microbiological culture of tracheal secretions and by asking the opinion of both a microbiologist and infectious disease specialist. Daily procalcitonin monitoring has been shown to be a good diagnostic tool to identify patients at an increased risk of infection and a complicated postoperative course following PEA.18 Using these criteria, we diagnosed one patient in the control group with VAP, and he received antibiotic treatment. Other limitations include the limits of high and low cuff pressure that we used for this study, which we agree were safe by virtue of protecting the trachea from pressure injury.3,5,6 Finally, the volume and viscosity of diluted methylene blue that we injected into the hypopharynx cannot be identical to those of secretions in the mouth in real life.
We conclude that regular monitoring and adjustment of tracheal tube cuff pressure during cooling and warming on CPB and especially before and after DHCA may prevent silent aspiration of pharyngeal secretions. We believe that this simple and effective process should become standard in DHCA. Future work is needed to test the effectiveness of different designs of, and materials used in, tracheal tubes, and also whether tubes that contain a closed system for suctioning material from the pharynx or the trachea have a role to play in cardiac surgery. Moreover, a separate study of other outcomes is required to answer important questions concerning the impact of tracheal tube cuff pressure control on both postoperative mechanical ventilation and frequency of postoperative pneumonia.
Acknowledgements relating to this article
Assistance with the article: none.
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Conflicts of interest: none.
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