Diagnostic and Therapeutic Strategies for Hypercarbia in Elderly Patients Undergoing Prolonged Retroperitoneoscopic Surgery ——The Role of TcPCO2 and PEEP

Background: Retroperitoneal laparoscopy provides less morbidity and faster recovery period. However, long-term pneumoperitoneum increases the risk of hypercapnia that may induce severe postoperative complications, especially in elderly patients. Our study aims at investigating the sensitivity and reliability of continuous transcutaneous carbon dioxide (TcPCO2) monitoring in diagnosing hypercapnia during retroperitoneoscopic surgery in elderly patients and evaluating the effect of positive end-expiratory pressure (PEEP) against retroperitoneum induced hypercapnia.

Methods:  Fifty-five patients aged over 65 years who were scheduled for selective retroperitoneoscopic surgery under general anesthesia were enrolled. The correlations between TcPCO2, end-tidal partial pressure of CO2 (PETCO2)  and arterial CO2 (PaCO2) were evaluated before pneumoperitoneum as well as 30 and 60 minutes after establishment of pneumoperitoneum (time 0, 1 and 2), respectively. Patients were randomly assigned to 5 groups accepting different levels of PEEP: 0, 4, 6, 8 and 10 cm H2O (group I, II, III, IV and V). PaCO2 and PETCO2 were measured at 80 minutes following pneumoperitoneum (time 3). Heart rate (HR), arterial pressure, airway pressure were evaluated throughout surgery.

Results: There was a significant correlation between TcPCO2 and PaCO2 (r=0.87, P<0.01), but the correlation between PETCO2 and PaCO2 was lessened with prolonged pneumoperitoneum. The consistency limit (mean±2SD) between PaCO2 vs. TcPCO2 and PaCO2 vs. PETCO2 was (-2.86, 5.46) and (-1.61, 20.11) mm Hg, respectively. A difference of ≤5 mm Hg happened in 96% results of PaCO2 vs. TcPCO2 and 32% of PaCO2 vs. PETCO2 (P<0.01). After the use of PEEP, the PaCO2 was increased in group I and II, sustained in group III, but decreased in group IV and V (P<0.05). In addition, PEEP restored the correlation between PETCO2 and PaCO2(r=0.6, P<0.01, N=55). The hypercapnia induced enhancement of mean arterial pressure (MAP) and HR was normalized by 10 cm H2O PEEP although the airway plateau pressure (PPLAT) and airway pressure peak (PPEAK)  values were elevated.

Conclusions: TcPCO2 may be used as an alternative non-invasive monitoring to predict the PaCO2 levels in elderly patients undergoing long-term retroperitoneoscopic surgery. PEEP (10 cm H2O) combined with low tidal volume (VT=7 ml/kg) ventilation provides a therapeutic approach to ameliorate pneumoperitoneum -induced hypercapnia in these patients.

Retroperitoneal laparoscopy plays a special role in urinary surgery for elderly patients due to the advantages of less injury, faster postoperative recovery (1), and low risks in tumor cells proliferation (2). However, carbon dioxide insufflation during laparoscopic surgery may cause respiratory acidosis and refractory hypercapnia that may lead to lethal complications, such as perioperative decompensation, especially in elderly patients. Thus it is necessary to establish an accurate monitoring approach that effectively prevents hypercapnia.

Transcutaneous partial pressure of carbon dioxide (TcPCO2) is a noninvasive method to monitor CO2 in microcirculation in a real-time manner. It has been used to reflect the arterial CO2 (PaCO2) in multiple clinical scenarios. When the end-tidal partial pressure of CO2 (PETCO2) is disturbed by increased intrathoracic pressure, severe cardiac or pulmonary diseases, etc., TcPCO2 becomes a valuable supplement to PETCO2 (3). However, the efficacy of TcPCO2 in predicting PaCO2 in elderly patients with complex ventilation parameters and declined pulmonary function during retroperitoneal laparoscopy has not yet been well understood.

Hypercapnia can be corrected by moderately excessive ventilation. However, in retroperitoneal laparoscopy, moderately excessive ventilation is not sufficient to improve the lung function and reduce PaCO2, in addition, it may increase the incidence of airway barotrauma and impede blood reflux and hemodynamic stability (4). Positive end expiratory pressure (PEEP) can be applied to prevent alveolar atrophy or collapse, reduce pulmonary arteriovenous shunting, thus improving ventilation/blood flow ratio and diffusion function.

The main goal of this study was to evaluate the correlation between PaCO2 and TcPCO2, assess the correlation between PaCO2 and PETCO2 during prolonged retroperitoneoscopic surgery, and investigate the role of PEEP in treating hypercapnia.

Patients and Ethical Approval
The study was conducted at the Department of Anaesthesiology, Xuanwu Hospital, Beijing, China, between 1 October 2011 and 31 August 2012. Fifty-five patients aged 65-85 years who were graded as American Society of Anaesthesiologists physical status (ASA) I-II and  were scheduled for elective urologic surgery with retroperitoneal laparoscope under general anesthesia were enrolled. Patients with special skin conditions unsuitable for TcPCO2 monitoring were excluded. Cases were removed from the study if the surgical time was less than 80 minutes or they switched from a surgical approach to another one.

The study was approved by the Ethic Committee of Xuanwu Hospital, and informed consents were signed by all the recruited patients.

Anesthesia and Monitoring
All patients accepted general anesthesia. Vein access in the upper limb was obtained prior to anesthesia, electrocardiogram (ECG), heart rate (HR), pulse oxygen saturation (SpO2), non-invasive blood pressure (NIBP), PETCO2 and nasopharyngeal temperature (NT) were continuously detected via a multifunctional monitor (AS/5, Datex-Ohmeda, Finland). Sedation was monitored by Bispectral index (BIS, Covidien, MA,  USA) and maintained between 40-60 during surgery. Nasopharyngeal temperature was controlled between 36-37 ℃ by an automatic heating blanket and heated air device. Blood gas analysis was performed with i-STAT system (Radiometer, Denmark) after induction of general anesthesia. TcPCO2 was monitored with a TCM4 system (Radiometer, Denmark). All the monitor parameters were calibrated regarding to the manual instructions prior to anesthesia. Rapid sequence induction was performed with midazolam 0.02 mg/kg, fentanyl 2 µg/kg, etomidate 0.15 mg/kg and cisatracuriumbesylate 0.15 mg/kg in proper order, endotracheal intubation was performed and mechanical ventilation was established. During operation, anesthesia was maintained with propofol (3-6 mg/kg/h), remifentanyl (0.025-0.1 µg/kg/min), and cisatracuriumbesylate (0.05-0.1 mg/kg/h). Intraoperative fluid therapy followed the “4-2-1 Principle” with a ratio of 1:1 for crystalloid versus colloids to accomplish physical requirements. Intraoperative blood loss was supplemented with an equal amount of colloid fluid. Before pneumoperitoneum, ventilation parameters were set as f 12-22 times/minute, VT 6-8 ml/kg, I:E ratio 1:2, inhaled fraction of oxygen concentration 40% (FiO2), PETCO2 35-45 mm Hg (4). Pneumoperitoneum was established at 30 minutes after the stabilization of  TcPCO2 to reach a stable TcPCO2 equilibrium (3, 5). CO2 pressure in pneumoperitoneum was maintained at 15 cm H2O through the surgery. When PaCO2 was over 55 mm Hg after pneumoperitoneum, the ventilation parameters were changed as follows: VT  7 ml/kg, and f 17 times/minute. TcPCO2, PETCO2, PaCO2 values were collected before pneumoperitoneum as well as 30 and 60 minutes after establishment  of pneumoperitoneum (T 0, 1 and 2).

After T2, patients were randomly assigned to 5 groups receiving different levels of PEEP: 0, 4, 6, 8 and 10 cm H2O, respectively (group I, II, III, IV and V, N=11 in each group). PaCO2, PETCO2, NIBP, HR, airway plateau pressure (PPLAT), airway pressure peak (PPEAK), and PaO2 were recorded. The indication of administration of vasoactive drugs was as follows: NIBP beyond the range of 90-160/40-95 mm Hg or HR beyond the range of 50-120 beats/minute. The data of aforementioned monitoring parameters were collected at 20 minutes following the PEEP (80 minutes after pneumoperitoneum, T3).

Statistical Analysis
According to the preliminary experiment, a sample size of 11 patients per group was needed such that 30% or more difference in PaCO2 could be detected between two groups with TypeI error of 0.10 and TypeII error of 0.20. Data were expressed as mean±standard deviation ([X]±S) and was analyzed by SPSS 13.0. The correlation of TcPCO2 with PETCO2 and PaCO2 was evaluated with Pearson analysis, respectively. The consistency of TcPCO2 with PETCO2 and PaCO2 was evaluated by Bland-Altman method, respectively. One-way ANOVA and q-test were applied for the comparison among groups at a given level of PEEP. Repeated measure t-test was used for the comparison in the same group at different time points. P<0.05 was considered as statistical significance.

In 55 patients undergoing retroperitoneal laparoscopy, 7 patients were subject to radical nephrectomy, 10 patients were assigned to partial nephrectomy, 18 patients received resection of adrenal gland tumor, and 20 patients accepted fenestration for renal cysts. Demographic data were displayed in table 1.

The Correlation Between TcPCO2, PETCO2 and PaCO2
With prolonged time of pneumoperitoneum, the difference between PETCO2 and PaCO2 increased gradually with rise in PaCO2, and no overall correlation was shown between PaCO2 and PETCO2 (Figure 1, Figure 2). The difference between TcPCO2 and PaCO2 was not affected by duration of pneumoperitoneum (Figure 1), and there was a significant correlation between TcPCO2 and PaCO2 regarding to all the three time points, with the correlation coefficient (r) of 0.87 (P=0.000). The correlation coefficient of correlation of TcPCO2 and PaCO2 at time 0, 1 and 2 were 0.74 (P=0.000), 0.78(P=0.000) and 0.80 (P=0.000), respectively. However, significant correlation between PETCO2 and PaCO2 was only found at time 0 and 1, r = 0.75 (P= 0.000) and 0.54 (P = 0.000), respectively (Figure 3).

The Consistency Among TcPCO2, PETCO2 and PaCO2
Among all the data that were collected at 3 time points, 96% of results of TcPCO2 and PaCO2 showed a difference ≤5 mm Hg, which was only seen in 32% results of PETCO2 and PaCO2 (P=0.023) (Figure 4).

PEEP Affects PaCO2 Level During Pneumoperitoneum
The PaCO2 level was significantly related to the level of PEEP. At twenty minutes following PEEP, PaCO2 level was increased in group I and II (P=0.012), with a less increase in group II (P=0.031). However, PaCO2 level was decreased in group IV (P=0.013) and further decreased in group V (P=0.017) (Figure 5).  

PEEP Affects Blood Pressure and Heart Rate During Pneumoperitoneum
The hemodynamic data showed both MAP and HR levels were increased in group I but decreased in group IV and V following PEEP compare to the baseline levels (P=0.018, 0.008, 0.003, respectively, Figure 6). There was also an increase in MAP in group II after PEEP (P=0.034). The strongest decline in MAP and HR values occurred in group V, but it was still in the range of ±20% of baseline values.

Pneumoperitoneum and PEEP Influences the Airway Pressure and PaO2
The values of PPLAT and PPEAK increased in proportion to the level of PEEP (P=0.008, 0.007 respectively, Figure 7A), while the values of PPLAT and PPEAK in group V were still under 35 cm H2O. PaO2 value, which stands for the oxygenation function, changed with the values of PPLAT and PPEAK (P=0.003, 0.006, respectively, Figure 7B).

PEEP Restores the Correlation Between PETCO2 and PaCO2
To investigate whether PEEP affects the accuracy of PETCO2, we evaluated the correlation between PETCO2 and PaCO2 at 20 minutes following PEEP. According to the  evidence from figure 8 and table 2, at 60 minutes of pneumoperitoneum, no correlation between PETCO2 and PaCO2 was found in group II, III, IV and V (PEEP applied was above 0 cm H2O, P=0.075), but their correlation were observed at  20 minutes following PEEP, and 80 minutes after pneumoperitoneum (correlation coefficient r=0.62, P=0.001, N=44). At 80 minutes after pneumoperitoneum, as the value of PEEP applied increased, the correlation coefficient between PETCO2 and PaCO2  elevated in sequence: r IV/V> r IIIIV> rII/III.

The retroperitoneal laparoscopic surgery significantly improves postoperative outcomes due to less invasiveness compared to traditional open abdominal surgeries. However, due to the large area of CO2 contact and abundant blood supply in the loose connective tissue (6), CO2 gas was rapidly absorbed, more severe hypercapnia was prone to happen (7).

Nowadays, there are both noninvasive and invasive techniques of measuring blood CO2 content. PaCO2 and PETCO2 are commonly used methods, while TcPCO2 has been initiated recently. Arterial blood gas analysis is the gold standard for measuring PaCO2, however, it is invasive, cumbersome and time-consuming when multiple measurements are required. In normal circumstances, the difference between PETCO2 and PaCO2 is a constant, thus PETCO2 can provide indirect estimates of PaCO2. However, in patients with complicated coexisted diseases, PETCO2 is reliable in predicting the PaCO2 decreases (8). In particular, during the retroperitoneal laparoscopic surgery, the excessive ventilation may increase intrathoracic pressure, reduce pulmonary blood flow, and increase proportion of dead space ventilation. Thus, CO2 partial pressure difference (PaCO2-PETCO2) at the end of expiration will significantly increase (3, 9). TcPCO2 causes the temperature of skin surface increase to increase the blood flow velocity in capillary, resulting in arterialization. Higher solubility and diffusivity of CO2 are used to measure the concentration of CO2 dispersing from arterialized capillaries in skin, and furthermore to predict PaCO2. In our study, the skin at the flexor side of brachioradialis was monitored to obtain stable and accurate data. It has been indicated that TcPCO2 can accurately (11-15) predict PaCO2 in a real-time manner (16), and has been widely used (8). The most important thing  is that TcPCO2 is a valuable supplement to PETCO2 monitoring in patients with a large gap between PaCO2 and PETCO2 and in those concurrently requiring continuous accurate non-invasive control of CO2 levels (4, 8, 9). But it has also been shown that TcPCO2 -PaCO2 difference will increase (8) in the following settings: PaCO2 above 60 mm Hg (16), hypoperfusion in measurement site, shock, edema, thick skin and  vasocontractive drugs.

In this study, 3 time points were chosen to analyze the correlation between PaCO2 and PETCO2: before pneumoperitoneum (baseline), 30 minutes [when CO2 absorption was the fastest (7)] and 60 minutes [when PaCO2 was relatively stable (7)] after establishment of pneumoperitoneum. Prior to pneumoperitoneum, there was a significant correlation between PaCO2 and PETCO2. After establishment of pneumoperitoneum, the hyperventilation setting (small tidal volume and high frequency) was used (10) to increase pulmonary ventilation volume. Due to the increased dead space ventilation and decreased pulmonary blood flow, PETCO2 increased as well and correlation between PaCO2 and PETCO2 was lost. According to our results, in elderly patients who underwent retroperitoneal laparoscopic surgery, it is not reliable to use PETCO2 to predict the PaCO2 level.

Our results indicated that significant correlation between TcPCO2 and PaCO2 still existed until 60 minutes of insufflation. Therefore, TcPCO2 may effectively predict the value and change trend of PaCO2. TcPCO2 value was not significantly affected by intrathoracic pressure, age-related changes in skin and subcutaneous circulation, pneumoperitoneum and hyperventilation modes in laparoscopic surgeries. Further evaluation using Bland - Altman method on consistency of TcPCO2 and PETCO2  with PaCO2 was performed and the maximum measurement error allowed clinically was assumed as plus or minus 5 mm Hg (17). Our results showed a poor correlation existed between PETCO2 and PaCO2 in retroperitoneal laparoscopic surgery, while TcPCO2 was highly correlated with blood gas PaCO2, hence it could be a good alternative measurement of blood CO2 level (17).

Studies by Mohsen et al. (18) showed that mild hypercapnia (PaCO2 45-53 mm Hg) provided a slight effect on cardiopulmonary function, while moderate to severe hypercapnia (PaCO2 54-70 mm Hg) may result in a significant change of cardiopulmonary function. In elderly patients with impaired organ function and  compensatory mechanism,  the tolerance to refractory hypercapnia drop dramatically. Intractable hypercapnia without effective treatment may further lead to acidosis, cause systemic inflammatory response syndrome and even multiple organ function failure (19-22). On the other hand, refractory hypercapnia may affect the cerebral oxygen saturation and increase the risk of delayed postoperative awakening in elderly patients.

It has been recognized that moderate excessive ventilation can correct CO2 accumulation and treat intractable hypercapnia. Moderate excessive ventilation, which means an increase of 10-15% in minute ventilation, is usually achieved by increasing tidal volume or breathing rate (23).

In elderly patients, certain lesions in small airways may exist. Insufflation easily induces increase in physiological dead space due to limited lung volume. High volume plus low frequency ventilation was considered capable of treating CO2 accumulation in elderly patients, but the improvement was not obvious (24); Further comparison of VA/Q ratio before and after insufflation was performed, the results indicated that this VA/Q ratio still significantly fell after insufflations. This suggested that high volume ventilation was not sufficient to improve lung function; on the other hand, blindly increasing the ventilation volume would increase the possibility of airway injury, affect the venous reflux and damage hemodynamic stability (24). Therefore, the small tidal volume plus high frequency ventilation strategy may be a better choice (25).

PEEP means that the ventilator produces a positive pressure higher than the atmospheric pressure at the end of expiration. PEEP could prevent alveolar atrophy or collapse, increase functional residual capacity (FRC) by opening up closed alveolus, decrease arteriovenous shunt, and restore ventilation/blood flow ratio and diffusion function. In that case, respiratory function could be improved in elderly patients with lung diseases (26). However, an even higher level of PEEP will induce an obvious elevation in airway pressure or intrathoracic pressure, which leads to ventilation injury and declined cardiac output.

Recently, a series of researches  have recommended that small tidal volume (5-7 ml/kg) with a certain level of PEEP could be a safer and effective ventilation strategy for elderly patients (7). Unfortunately, It is still controversial which level (high [4, 27, 28] or low [25, 29]) of PEEP is proper.

In our study, comparison of PaCO2 before and after PEEP was performed. Our data suggested that small tidal volume (7 ml/kg) with PEEP could, to a certain extent, effectively reverse pneumoperitoneum induced hypercapnia, and PEEP of 4-10 cm H2O was more effective  compared to higher PEEP  levels (Figure 5).
Until now, the therapeutic role of PEEP in hypercapnia has been confirmed. We continued to investigate the adverse effects of PEEP (4-10 cm H2O), and its impact on pulmonary and cardiovascular system was used as indicators.

In this study, adequate depth of anesthesia, proper analgesia and muscle relaxtion were maintained during operation to eliminate their effect on pulmonary and cardiovascular system. Our results showed that MAP and HR stopped to elevate in group II and III after application of PEEP, this illustrated that the effect of PEEP (4-6 cm H2O) was enough to compensate the impact of hypercapnia. Furthermore, MAP and HR decreased more significantly in Group IV and V, indicating that higher levels of PEEP (> 8 mm Hg) had reversed the effect of hypercapnia and relieved the overactivation of sympathetic nerves. Another possible explanation is that high level of PEEP could increase intrathoracic pressure and damage venous reflux, resulting in drop in cardiac output. In spite of this, the decrease in MAP or HR was still within the clinical acceptable range (30) and did not harm the perfusion of vital organs in elderly patients. Our data demonstrated that PPLAT and PPEAK increased gradually with application of PEEP. The average value of PPEAK was over 30 mm Hg in group IV and V, simultaneously, mean PPLAT was above 25 mm Hg in those two groups. It has been recognized that PPLAT>25 mm Hg is the main risk factor for barotrauma, indicating that PEEP>8 cm H2O may increase risk of ventilator-induced lung injury. By contrast, several meta-analysis focused on reducing  postoperative pulmonary complications by different ventilation strategies. Their results recommended that a higher level of PEEP (3 to 12 cm H2O) is more advantageous to prevent postoperative lung injury, infections and atelectasis (31). Our data also indicated that 4 to 10 cm H2O of PEEP could effectively improve intraoperative oxygenation without any significant adverse hemodynamic effects in elderly patients. So in general, a PEEP value of 10 cm H2O could be accepted, which is a  preferred strategy for its better effect of reversing hypercapnia.

To conclude, the strategy to ventilate patients using small tidal volume (7 ml/kg) plus 10 cm H2O PEEP can effectively alleviate the hypercapnia without obvious adverse effects in retroperitoneal laparoscopic surgery. A point worth emphasizing is that only relatively healthy elderly patients (ASA I -II ) were enrolled into our study and the ventilation strategy could just induce a certain extent decrease in PaCO2 after pneumoperitoneum. In elderly patients with moderate to severe lung disease or perioperative severe hypercapnia, further studies are still needed to test the efficacy and safety of the forementioned strategy. Several impacting factors, such as preoperative status, operation time and insufflation pressure, should be carefully considered.

After 60 minutes of pneumoperitoneum, PETCO2 and PaCO2 became unmatched. However, at 20 minutes after the application of PEEP, their consistence restored and PETCO2 - PaCO2 correlation coefficient increased with the level of PEEP. The increase in  PETCO2 - PaCO2 difference was more marked due to the impact of pneumoperitoneum, lateral clasp-knife position, and shunt in the lung. At this point, the further increase in ventilation frequency would shorten exhalation time and worsen the CO2 expiration. The use of PEEP was a better choice to solve this problem. This strategy could effectively narrow the gap between PETCO2 and PaCO2,  and restore their consistence. This effect was proportional to the level of PEEP in the range of 4-10 cm H2O.

In conclusion, in elderly patients subject to retroperitoneal laparoscopic surgery for more than 1 hour, correlation and consistency between PaCO2 and TcPCO2 are higher compared to PETCO2. Hence, TcPCO2 can effectively predict PaCO2 level. In addition, during this kind of surgery, the ventilation strategy using small tidal volume (7 ml/kg) plus 10 cm H2O PEEP can be a safe and effective choice to treat pneumoperitoneum-induced hypercapnia, and restore the consistency between PETCO2 and PaCO2 .