|Year : 2013 | Volume
| Issue : 2 | Page : 53-57
Nephrectomy in children: Comparison of stress response to laparoscopic and open methods
Virender Sekhon1, Prema Menon1, Sunil Arora2, K. L. N. Rao1
1 Department of Pediatric Surgery, Advanced Pediatric Center, Chandigarh, India
2 Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||21-Mar-2013|
Department of Pediatric Surgery, Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research, Chandigarh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Aim: To evaluate and compare the extent of surgical stress following laparoscopic nephrectomy (LN) and open nephrectomy (ON) in children. Materials and Methods: Twenty consecutive children undergoing nephrectomy were randomized to LN or ON groups. Acid-base balance, blood glucose, acute phase proteins (C-reactive protein [CRP]) and inflammatory markers (interleukin-6 [IL-6]) were measured pre-operatively, as well as 4 and 24 h after surgery. The differences between the two groups were analyzed statistically (significance value for P < 0.05). Results: The overall acid base status was more stable in LN. The fall in pH 4 h after surgery was more in ON (P = 0.440) and the difference in pH in ON 4 h and 24 h post-operatively was statistically significant (P = 0.002). In LN, significant difference was found in the base excess mean pre-surgery (mean -3.280 mEq/L) and 4 h post-surgery (mean -7.480 mEq/L) (P = <0.05), as well as between 4 h and 24 h after surgery (mean -2.660 mEq/L) (P = 0.011).The acute rise in CRP 24 h post-operatively in the ON (88.972 mg/L) was significantly higher when compared to both the pre-operative and 4 h post-operative values (P < 0.05). This rise was however, not statistically significant when compared to the 24 h post-operative value in LN (46.399 mg/L) (P = 0.062). The rise in IL-6, 24 h post-procedure in LN (mean 44.444 pg/ml) was statistically lower than that in the open group (mean 343.333 pg/ml) (P = 0.041). Conclusions: The stable acid-base status and lesser rise of CRP and IL-6 in LN lead to the conclusion that surgical stress caused by LN is less than ON.
Keywords: Children, laparoscopic nephrectomy, open nephrectomy, stress response
|How to cite this article:|
Sekhon V, Menon P, Arora S, Rao K. Nephrectomy in children: Comparison of stress response to laparoscopic and open methods. J Indian Assoc Pediatr Surg 2013;18:53-7
|How to cite this URL:|
Sekhon V, Menon P, Arora S, Rao K. Nephrectomy in children: Comparison of stress response to laparoscopic and open methods. J Indian Assoc Pediatr Surg [serial online] 2013 [cited 2020 Jan 24];18:53-7. Available from: http://www.jiaps.com/text.asp?2013/18/2/53/109352
| Introduction|| |
Laparoscopic surgery has recently emerged as an alternative to various types of open surgery. The proven advantages of any laparoscopic surgery are smaller incisions, less post-operative pain; faster recovery time and less hospital stay.  However, there have been few studies in the pediatric population analyzing the difference in surgical stress after nephrectomy by laparoscopic and open surgery. In the present study, we compared the stress response after laparoscopic nephrectomy (LN) and open nephrectomy (ON) with the measurement of pathophysiological markers, including blood gas analyzes, blood glucose, C-reactive protein (CRP) and serum interleukin-6 (IL-6), which have been shown to be markers reflecting the severity of surgical damage. ,,
| Materials And Methods|| |
This was a prospective study. Twenty cases posted for elective nephrectomy were randomized to undergo LN or ON. Children aged between 1-12 years, with American Society of Anesthesiologists grade 1-3 were included. Those with clinical suspicion of sepsis, major systemic illnesses, malignant conditions and conversion of LN to ON were excluded from the study.
All patients were fasting for 6 h pre-operatively, with a maintenance infusion of dextrose/saline and pre-medication were administered before surgery to allay undue anxiety. The operating room temperature was maintained between 26 and 28°C. All cases were performed under general anesthesia with endotracheal intubation and induction was performed using standard protocol. All patients were given a single standard dose of antibiotic at anesthesia induction. Catheterization and nasogastric tube drainage were done for all. The anesthesia induction to reversal time and operating time from incision to last suture was recorded.
For LN, patient was placed supine with a 30° elevation on the side of operation. Hassan's technique was used to gain intra-abdominal access and CO 2 at room temperature was used for insufflation, maintaining intra-abdominal pressure between 8 and 12 mm Hg at a maximum flow rate of 1 L/min. A 10 mm port was placed at the umbilicus and two 5 mm ports - one at the mid-point between xiphisternum and umbilicus, another at ipsilateral mid-clavicular line just below the umbilical level, were used. An additional 5 mm port was inserted in the flank if necessary. For ON, an extra-peritoneal antero-lateral transverse incision was used. Standard techniques of dissection were used for both LN and ON.
Post-operatively, the patient's vitals were monitored. All patients were kept nil per oral for the first 24 h after surgery. Ambulation was advised from the 1 st post-operative day. Antibiotics were given during the period of stay- intravenous for the first 48 h followed by oral for another 3 days. Intravenous paracetamol and tramadol were given for analgesia for the first 48 h, followed by oral paracetamol. Dressing was removed 24 h after surgery and wound was examined daily for any infection.
Heparinized blood samples were collected pre-operatively a day before surgery and 4 h and 24 h post-operatively, for analysis of acid-base balance, blood glucose, acute phase protein CRP and inflammatory marker cytokine IL-6. Blood gas analyzes was done using the Roche OMNI-S analyzer (Roche Diagnostics, Switzerland) with integrated auto QC drawer option. Serum CRP and IL-6 were measured using an enzyme linked immunosorbent assay (ELISA). The samples for measuring IL-6 were stored at a temperature of −80°C until the time of analysis. Manufacturer's instructions on the ELISA kit were followed directly on the samples.
The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, version 16). Means were compared using Student's t-test and Mann-Whitney test. Chi-square and Fisher's exact test were used for comparing proportions. For time-related variables repeated measure ANOVA was applied followed by one-way ANOVA or Wilcoxon signed rank-test, whichever, applicable. All statistical tests were two-sided and were performed at a significance level of P = 0.05.
| Results|| |
The clinical characteristics of patients who underwent LN and ON are summarized in [Table 1]. The operating time and anesthesia time were significantly higher in the laparoscopic group as compared to the open group (P < 0.05), although some of the confidence intervals are wide. The side distribution (right/left) in LN group was 7/3 versus 3/7 in ON group. There were no intra-operative complications in either group.
The distribution of patients as per the diagnosis within the two groups is given in [Table 2]. There was no incidence of post-operative wound infection in either group. The comparison of estimated marginal means of pH, pCO2, HCO3, base excess (BE), glucose, CRP and IL-6 in open versus LN groups is plotted in [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]. The blood pH showed a fall 4 h post-operatively in both LN and ON groups, followed by a rise to near normal values 24 h later. The change in pH in ON group between 4 h (7.296) and 24 h (7.353) post-operatively was statistically significant (P = 0.002). Overall, pH remained more stable in LN patients.
There was retention of CO 2 in the ON group 4 h after the procedure (mean 43.660 mmHg), which tended to normalize 24 h later (mean 38.640 mmHg). Contrary to this, there was a fall in pCO 2 4 h after LN (mean 37.120 mmHg), which rose to a mean of 40.830 mmHg, 24 h later. None of these values were statistically significant. HCO 3 remained fairly constant in the ON group 4 h after surgery (mean 19.400 mEq/L) and rose insignificantly after 24 h (20.79 mEq/L).The LN group showed a statistically significant fall in HCO 3 4 h after surgery (mean 18.322 mEq/L, P = 0.002) when compared to the pre-operative levels (22.58 mEq/L), followed by a rise to a mean of 21.07 mEq/L.
The BE followed a similar pattern of initial rise and subsequent fall in both study groups. In the ON group, the mean at 4 h post-operatively was -12.390 mEq/L and that at 24 h was-5.000 mEq/L. In the LN group, significant difference was found in the mean pre-surgery and 4 h post-surgery (-7.480 mEq/L) values (P ≤0.05), as well as between 4 h and 24 h after surgery (mean -2.660 mEq/L, P = 0.011). Both ON and LN groups showed closely related mean blood glucose values at all times during the study, which remained within the normal range. The mean pre-operative blood glucose (92.30 mg/dL) in the LN group rose significantly to 123.90 mg/dL 4 h after surgery (P = 0.002).
The baseline CRP value remained stable up to 4 h after surgery in both groups, with a mean of 2.786 mg/L in the ON and 5.499 mg/L in the LN group. The acute rise in CRP 24 h post-operatively (88.972 mg/L) in the ON group was significantly higher when compared to both the pre-operative and 4 h post-operative values (P < 0.05) of the same group. This rise was however, not statistically significant when compared to the 24 h post-operative value in the LN group (46.399 mg/L, P = 0.062). The pre-operative IL-6 levels were undetectable in both study groups. The difference in rise in both groups at 4 h (ON 134 pg/ml, LN 17.777 pg/ml) and 24 h (ON 343.333 pg/ml, 44.444 pg/ml) after surgery was statistically significant (P = 0.041).
| Discussion|| |
The widespread implementation of laparoscopic surgery has been fostered by the assumption that it is associated with a dampening of the stress response to surgery. Several studies have been undertaken in adults in order to investigate its physiological effects and compare open and laparoscopic methods.  However, this assumption regarding the impact of laparoscopic surgery on endocrine and metabolic responses in children has not been widely tested. 
Nephrectomy patients were best suited for studying the surgical stress response in our settings, given their ease of availability and our proficiency in managing them. The response to surgical stress involves complex interactions among the nervous, endocrine, immune and hematopoietic systems,  characterized by hyperglycemia and a decrease in insulin and a systemic response including fever, leukocytosis and production of acute phase proteins.  Cytokines and hormones are considered important mediators in this response, among which IL-6 has been demonstrated to be a useful marker reflecting surgical stress.  Therefore, in this study, we measured the serum levels of these mediators (acid-base balance, glucose, CRP, IL-6) to objectively compare surgical stress between LN and ON.
The renal handling of electrolytes influences acid-base balance. The fall in pH 4 h after surgery in both groups is a manifestation of the surgical stress, which was more in the open group. The increased post-operative wound pain, shallow respiration and hence hypoxia caused by open surgery  is reflected in the rise in pCO 2 values in this group 4 h post-operatively. On the contrary, the CO 2 retention due to pneumoperitoneum induced during laparoscopy is reflected in rising pCO 2 values 24 h after laparoscopy in our study. It is to be noted here, that CO 2 absorption from the abdominal cavity during laparoscopy in children is different than in adults.  Though the HCO 3 and BE levels did not show any significant changes in the open group, the mean pH remained more stable in the laparoscopy group. This might represent the lesser tissue trauma in this subset of patients. In a study by Luo et al. on operative stress response after laparoscopic cholecystectomy (LC) compared to open surgery, pH levels were much lower on the 1 st post-operative day and there was significant rise in the values of HCO 3 and BE on the 3 rd post-operative day in the LC group.  This might indicate that the stress response to surgery extends beyond the first 24 h, as can be extrapolated from our study also.
The comparable increase in glucose during both laparoscopic and open techniques in our study, indicates that considerable activation of the neuro-endocrine axis does occur during laparoscopy in spite of the absence of a substantial skin incision. This is in agreement with Bozkurt et al. in whose study blood glucose and other metabolic stress parameters like cortisol, prolactin, and epinephrine increased significantly intra-operatively in all the adult studies (both randomized and non-randomized) and the response was similar both for laparoscopic and open groups. ,
The hyper-metabolic state in response to surgical trauma is directly linked to the activation of sympathetic nervous system and the synthesis of acute phase proteins mainly CRP.  The level of CRP usually reaches a peak level on post-operative days 2 or 3 in adult patients.  In our study, CRP levels started rising 4 h after surgery and continued to rise 24 h later. Li et al. proposed in their study on appendectomy in children that during laparoscopic surgery, the intra-abdominal organs were not exposed to external air; therefore, they do not have any heat loss and the acute-phase response was consequently reduced. 
Many previous studies have shown that the increase of circulating IL-6 serum levels were proportional to the severity of surgical trauma. , The significantly higher rise of IL-6, 24 h post-operatively in the ON group as compared to the LN group in our study, may be a reflection of the same phenomenon. However, there are other reports which have found no significant differences between IL-6 levels of open and laparoscopic surgeries. A variable perioperative cytokine response in children during major surgery for non-inflammatory disease as reported by Hansen, et al.  is a plausible explanation.
We acknowledge the limitations of our study. The relatively small sample sizes of our surgical groups limit the inferences that can be applied to the clinical situation. More extensive clinical studies and inclusion of other immune and metabolic markers may be necessary to understand in more detail the significance of the surgical stress response to LN.
| Conclusion|| |
The stress response to surgery is complex. We found that the acid-base status as a whole remained more stable in the LN group as compared to the ON group in our study. Although the glucose levels remained comparable in both the groups, the lesser rise of CRP and IL-6 in the laparoscopy group indicates that the trauma caused by LN is less than that caused by ON.
The minimal tissue injury caused by the laparoscopic surgery results in a smaller and shorter acute phase response. Thus, our study revealed that LN was less invasive and induced less host stress response and metabolic disturbance compared with the traditional ON. The beneficial effects of laparoscopic surgery may therefore relate, in part, to less surgical stress in the immediate post-operative period.
| References|| |
|1.||Miyake H, Kawabata G, Gotoh A, Fujisawa M, Okada H, Arakawa S, et al. Comparison of surgical stress between laparoscopy and open surgery in the field of urology by measurement of humoral mediators. Int J Urol 2002;9:329-33. |
|2.||Bozkurt P, Kaya G, Altintas F, Yeker Y, Hacibekiroglu M, Emir H, et al. Systemic stress response during operations for acute abdominal pain performed via laparoscopy or laparotomy in children. Anesthesia 2000;55:5-9. |
|3.||Luo K, Li JS, Li LT, Wang KH, Shun JM. Operative stress response and energy metabolism after laparoscopic cholecystectomy compared to open surgery. World J Gastroenterol 2003;9:847-50. |
|4.||Matsumoto ED, Margulis V, Tunc L, Taylor GD, Duchene D, Johnson DB, et al. Cytokine response to surgical stress: Comparison of pure laparoscopic, hand-assisted laparoscopic, and open nephrectomy. J Endourol 2005;19:1140-5. |
|5.||Karayiannakis AJ, Makri GG, Mantzioka A, Karousos D, Karatzas G. Systemic stress response after laparoscopic or open cholecystectomy: A randomized trial. Br J Surg 1997;84:467-71. |
|6.||McHoney MC, Corizia L, Eaton S, Wade A, Spitz L, Drake DP, et al. Laparoscopic surgery in children is associated with an intraoperative hypermetabolic response. Surg Endosc 2006;20:452-7. |
|7.||Weissman C. The metabolic response to stress: An overview and update. Anesthesiology 1990;73:308-27. |
|8.||Vittimberga FJ Jr, Foley DP, Meyers WC, Callery MP. Laparoscopic surgery and the systemic immune response. Ann Surg 1998;227:326-34. |
|9.||Hendolin HI, Pääkönen ME, Alhava EM, Tarvainen R, Kemppinen T, Lahtinen P. Laparoscopic or open cholecystectomy: A prospective randomized trial to compare post-operative pain, pulmonary function, and stress response. Eur J Surg 2000;166:394-9. |
|10.||McHoney MC, Corizia L, Eaton S, Kiely EM, Drake DP, Tan HL, et al. Carbon dioxide elimination during laparoscopy in children is age dependent. J Pediatr Surg 2003;38:105-10. |
|11.||Nakamura M, Suita S, Yamanouchi T, Masumoto K, Ogita K, Taguchi S, et al. Cortisol and cytokine responses after surgery in different age groups of pediatric patients. Pediatr Surg Int 2003;19:194-9. |
|12.||Li P, Xu Q, Ji Z, Gao Y, Zhang X, Duan Y, et al. Comparison of surgical stress between laparoscopic and open appendectomy in children. J Pediatr Surg 2005;40:1279-83. |
|13.||Hansen TG, Tønnesen E, Andersen JB, Toft P, Bendtzen K. The peri-operative cytokine response in infants and young children following major surgery. Eur J Anesthesiol 1998;15:56-60. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2]