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Eur J Cardiothorac Surg 1998;14:107-112
© 1998 Elsevier Science NL

Chronic hypercapnia should not exclude patients from lung volume reduction surgery¹

^a Department of Cardiothoracic Surgery, University of Vienna, Währinger Gürtel 18–20, A-1090 Vienna, Austria
^b Pulmonary Department, Lainz Hospital, Vienna, Austria
^c Department of Anesthesiology, University of Vienna, Vienna, Austria

Received 28 September 1997; received in revised form 23 March 1998; accepted 12 May 1998.

Corresponding author. Tel.: +43 1 404005620; fax: +43 1 404005642; e-mail: Wilfried.Wisser@akh-wien.ac.at

	Abstract

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Objective: Chronic hypercapnia is still considered to increase the risk for perioperative mortality and therefore to be a contraindication for lung volume reduction surgery (LVRS). The aim of this study was to analyse the influences of hypercapnia upon postoperative outcome. Methods: The functional improvement (preop vs. 3 months postop) and clinical outcome was studied in 22 patients with chronic hypercapnia (preoperative arterial pCO₂45 mmHg) who underwent LVRS between 9/94 and 2/97 and were compared to all other patients (n=58) without hypercapnia. Data are expressed as the mean±SEM. Results: The 30-day mortality was 9.1% (2/22) in patients with chronic hypercapnia (HC) and 5.2% (3/58) in patients with normal arterial pCO₂ levels (control) (P=n.s). The stay on the ICU (3.5±0.8 vs. 2.1±0.3 days) and duration of chest drainage (7.3±1.2 vs. 7.2±0.8 days) was similar between both groups (HC vs. control) (P=n.s). The preoperative lung function (% of predicted) and blood gas (mmHg) parameters were significantly worse in HC patients compared to control patients. In both groups significant functional improvements were observed: FeV1 in the control group increased by 37% within the first 3 months (29.1±1.7% of predicted vs. 39.9±3.1% of predicted, P=0.0198). In the HC group, FeV1 increased by 73% which was even higher than in the controls (19.5±1.5% of predicted vs. 33.7±4.7% of predicted, P=0.0385). All patients of both groups who died perioperatively had a significantly higher severity of parenchymal destruction than those who survived (P=0.0277 and 0.0380, respectively). Conclusions: Patients with chronic hypercapnia alone, had no significantly higher mortality and morbidity, and therefore should not be excluded from LVRS. However, the presence of additional risk factors, such as homogeneity of disease, high degree of parenchymal destruction or pulmonary hypertension should be considered as contraindications for the procedure.

Key Words: Lung volume reduction surgery • Diffuse emphysema • Hypercapnia

	Introduction

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Severe emphysema markedly limits the well being and life span of afflicted patients. Lung volume reduction surgery (LVRS) has shown its capability to provide relief for markedly dyspnoeic patients and to improve lung function substantially [1] [2]. However, an important number of patients with emphysema additionally present with severe chronic hypercapnia, which has been considered to be a contraindication for LVRS [3] [4] [5] [6] in many centers. Therefore only few data about the functional improvement and outcome of this subset of patients exist in literature [7] [8] [9]. In our program of LVRS [2], where patients with chronic hypercapnia have not been categorically excluded, about 25% of all patients belonged to this subgroup.

The aim of this retrospective study was to analyse the functional outcome and perioperative morbidity and mortality of this group of hypercapnic patients and compare them to all other patients without hypercapnia, who underwent LVRS. Deriving from these observations it is intended to establish possible criteria and guidelines for acceptance of patients with chronic hypercapnia for LVRS.

	Materials and methods

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Patient demographics
Eighty consecutive patients (49 male, aged 56.9±1.3 years, range 39–79 years), who were referred, accepted for and underwent LVRS between September 1994 and February 1997 were enrolled in this retrospective study. Twenty-two patients had chronic hypercapnia preoperatively (arterial pCO₂45 mmHg, range 45–77.6 mmHg, mean 51.7±1.7 mmHg, median 51.3 mmHg, upper 95% mean 55.2 mmHg, lower 95% mean 48.3 mmHg) (group HC), the other 58 patients had normal arterial pCO₂ levels and served as controls (arterial pCO₂ ranged from 29–43.3 mmHg, mean 37.9±0.5 mmHg, median 38 mmHg, upper 95% mean 38.9 mmHg, lower 95% mean 36.9 mmHg). The preoperative patient demography and the surgical approaches are shown in Table 1.

Assessment
All patients underwent a complete clinical and morphometric workup preoperatively and 1, 3 and 6 months postoperatively [2]. Pulmonary function tests were performed, measuring the forced expiratory volume in one second (FeV1), vital capacity (VC), total lung capacity (TLC) and residual volume (RV). In addition, arterial blood gas testing and measurement of work of breathing and intrinsic PEEP [10] was performed. The morphometric assessment included the evaluation of the degree of heterogeneity and the severity of parenchymal destruction as described previously [11]. In case of suspected pulmonary hypertension, right heart catheterisation was performed.

The influence of each group upon postoperative outcome and complication rate was studied. A comparison between the two groups in terms of the functional improvement was performed.

Statistics
Comparisons between the two groups and between preoperative and postoperative data were performed with the Student t-test for unpaired and for paired data, respectively. The mortality rates were compared with Chi-Square testing. A P-value<0.05 was chosen as significant. Data are expressed as the mean±SEM.

	Results

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Operative mortality, morbidity and perioperative data
The mortality was 9.1% and 5.2% in HC and control groups, respectively (P=0.928). In the HC group two patients died 10 and 16 days after LVRS due to cardiorespiratory and hepatic failure, respectively. In the control group three patients died four, 19 and 18 after LVRS due to pulmonary edema, aspiration pneumonia and multi organ failure respectively.

Three patients (one in the control group, two in the HC group) required long term ventilatory support because of excessive pulmonary cachexia and weakness preoperatively. All three underwent tracheostomy and were successfully weaned from the respirator 23 days (control group), 17 and 66 days (cH group) after surgery.

The remaining patients (54 in the control group and 18 in the HC group) were extubated 6.7±4.2 and 2.9±0.8 h after surgery in HC and control groups, respectively (P=0.174). The mean stay on the intensive care unit was 3.5±0.8 days (1–11 days) in the HC group versus 2.1±0.3 days (1–11 days) in the control group (P=0.047). The length of the complete hospital stay showed no significant difference: 12.2±2.1 days versus 11.4±0.9 days in HC and control group, respectively (P=0.707).

Mean duration of chest drainage was 7.3±1.2 days in the HC group and 7.2±0.8 days in the control group (P=0.946).

Lung function testing
On spirometry, the preoperative values of FeV1, TLC and RV were significantly more compromised in the HC group compared to the controls. In both groups, FeV1 significantly increased ( Fig. 1 ), TLC and RV significantly decreased after surgery. Data are shown in Table 2. In the control group, FeV1 increased from 0.96±0.08 l/s preoperatively to 1.1±0.07, 1.22±0.12 and 1.17±0.11 l/s after 1, 3 and 6 months, respectively. In the HC group FeV1 increased from 0.61±0.07 l/s preoperatively to 0.85±0.08, 1.02±0.17 and 0.97±0.10 l/s after 1, 3 and 6 months respectively.

View larger version (16K): [in this window] [in a new window]   Fig. 1. Forced expiratory volume in 1 s (FeV1). For significance values, refer to Table 2. Dotted line, control group; solid line, HC group.

View larger version (14K): [in this window] [in a new window]   Fig. 2. Arterial pCO2 levels. For significance values and legend, refer to Table 2 and Fig. 1, respectively.

View larger version (15K): [in this window] [in a new window]   Fig. 3. Arterial pO2 levels. For significance values and legend, refer to Table 2 and Fig. 1, respectively.

The work of breathing decreased in the HC group from 1.49±0.11 J/l preoperatively to 0.89±0.05 J/l, 0.95±0.08 J/l and 0.88±0.06 J/l 1, 3 and 6 months postoperatively (P=0.001 vs. preoperative value). In the control group WOB decreased from 1.88±0.18 J/l preoperatively to 0.95±0.1 J/l, 1.15±0.25 J/l and 1.19±0.29 J/l 1, 3 and 6 months postoperatively (P=0.001 vs. preoperative value). No significant difference was calculated between the groups.

Morphological assessment
The distribution pattern of the severity of parenchymal destruction (SPD) and the degree of heterogeneity (DHG) are shown in Table 1.

Perioperative mortality and preoperative parameters
The differences of preoperative parameters when splitting patients into survivers and non-survivers is shown in Table 3. Only the severity of parenchymal destruction (SPD) was significantly worse in patients who died perioperatively in both groups, suggesting an impact upon perioperative mortality. FeV1 was significantly different in the whole patient collective only.

	Discussion

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As expected, LVRS substantially improved lung function parameters. In the control group FeV1 significantly increased by 37% within the first 3 postoperative months. Patients in the HC group showed an 73% increase in FeV1 within the first 3 months, which was significantly higher than in the control group. Six patients in the HC group had even a preoperative pCO₂ level greater than 55 mmHg (61.5±3.3 mmHg), but showed no difference in terms of functional improvement, compared to the others in the HC group. This observation is in contrast to some other reports in which the amount of functional improvement was just the opposite: Argenziano et al. [7] reported that patients with hypercapnia (n=8, pCO₂55 mmHg) had an 47%, patients (n=35) with pCO₂ levels less than 55 mmHg an 70% increase in FeV1. Keenan et al. [9] observed in 60% of hypercapnic patients `poor outcome'. The reason for this controversy remains speculative, but differences in the morphometric parameters (degree of heterogeneity and severity of parenchymal destruction) may be a possible explanation. In tendency, we found a superior functional improvement in patients with low preoperative FeV1. This is in context with Argenziano's observation, where patients with a FeV1 below 500 ml preoperatively had more functional improvement than others. Further studies may clarify the influence of the degree of heterogeneity upon functional improvement.

Analysis of the preoperative patient demographics evidenced that chronic hypercapnia has been associated with more functional impairment, although the only selection bias was an elevation of the arterial pCO₂ level of more than 45 mmHg. One would expect that this poor functional status would contribute to a higher rate of morbidity. However, our clinical data gave no evidence for statistical difference in terms of length of hospital stay, chest tube drainage and length of intubation. The only significant difference was found for the mean time on the intensive care unit, which was significantly longer in the HC group (3.5 days), compared to the controls (2.1 days).

Besides morbidity, perioperative mortality is an issue of concern in this subgroup of patients. Although the perioperative mortality rate of patients with chronic hypercapnia was higher, it did not significantly differ compared to the control group. In fact, both patients who died in the HC group had a pCO₂ level between 45 and 55 mmHg, no patient was lost in the subgroup of patients (n=6) with a pCO₂ level above 55 mmHg. A similar result was reported by Argenziano et al. [7] who observed no difference in mortality rates between patients with pCO₂ less or above 55 mmHg. On the other hand, a markedly higher risk of perioperative mortality in patients with hypercapnia was observed by Keenan et al. [9]. These differences in the results raise the question, if the risk of perioperative mortality can be attributed to the hypercapnia preoperatively alone. We therefore have analysed other possible preoperative risk factors. Splitting of both groups into survivors and those who died perioperatively, revealed several interesting facts (Table 3). The preoperative pCO₂ levels of surviving patients and those who died were similar in both HC and control groups, suggesting that pCO₂ did not influence the mortality rate. A contrary trend was observed for the preoperative FeV1. Although FeV1 did not differ between patients who died and those who survived in both groups, in the whole patient cohort, FeV1 was significantly worse in patients who died (P=0.0404). The most prominent impact however, was observed for the morphometry of emphysema in terms of severity of parenchymal destruction (SPD). In both groups SPD was significantly higher in patients who died perioperatively. For all other preoperative functional parameters no significant difference was calculated.

In addition to the severity of parenchymal destruction, some patients presented with further factors, which are supposed to increase the risk of perioperative mortality. Both patients in the HC group who died presented with marked pulmonary hypertension (mean PAP 32 and 38 mmHg, respectively), and one of them had a homogeneous type of emphysema in addition. Analysis of the three patients who died in the control revealed a similar risk profile: besides the significantly higher SPD, two patients had pulmonary hypertension and the third patient complete homogeneity of the emphysema. This preliminary experience suggests that the addition of pulmonary hypertension and homogeneity of emphysema may increase the mortality risk. Further studies will be needed to analyse its impact upon mortality.

In conclusion, patients with chronic hypercapnia although presenting with a significantly more compromised lung function preoperatively, had a significantly higher lung functional improvement after LVRS. Since no significantly higher morbidity and mortality was observed in these patients, they should be considered as potential candidates for LVRS. However, we feel that the presence of additional risk factors, such as a high degree of parenchymal destruction, homogeneity or pulmonary hypertension should exclude hypercapnic patients from surgery for safety reasons.

Deriving from these observations, we presently adhere to the following acceptance criteria for patients with chronic hypercapnia: (1) pronounced heterogeneity of disease, (2) areas of well preserved lung structure and therefore a lower degree of severity of parenchymal destruction, (3) absence of additional risk factors.

	Footnotes

 
Presented at the 11th Annual Meeting of the European Association for Cardio-thoracic Surgery, Copenhagen, Denmark, September 28 – October 1, 1997.

	Appendix A. Conference discussion

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Dr Zenati (Pittsburg, PA, USA): I wondered if you looked at the DLCO in you study? The reason I am asking is because our group has shown that actually the hypercapnia and percent predicted DLCO, less than 25, the combination of the two actually, was a predictor of poor results.

Dr Wisser: Unfortunately, we could not analyze it because we just started to analyze the DLCO preoperatively a year ago, so we have not got all numbers of all patients and therefore unfortunately, no further analysis was possible for that question.

Dr Lerut (Leuven, Belgium): Did you experience, during the operation, especially in the groups who had bilateral VATS and where you have to have collapse, more problems in monitoring the patients?

Dr Wisser: In the hypercapnic group?

Dr Lerut: Yes.

Dr Wisser: No, not really.

Dr Svenevig (Oslo, Norway): The mean pCO₂ for the patients that you included in the study was almost 52, that is almost 7 kPa. What was the highest value that you accepted and is there and upper limit?

Dr Wisser: The pCO₂ levels ranged up to 67 mmHg. Actually we considered no limit. Your probably question if there are differences within the group. Because of small numbers, we have only 22 patients with hypercapnia, we could not analyze it properly. But just looking at them, there is pretty much no difference if they have 52 or 60.

	References

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5. Naunheim K.S., Ferguson M.K. The current status of lung volume reduction operations for emphysema. Ann Thorac Surg 1996;62:601-612.[Abstract/Free Full Text]
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