European Journal of Cardiovascular Medicine

Laparoscopic surgeries require creation of pneumoperitoneum (PNP), by insufflation of gases like carbon dioxide (CO₂) into the peritoneal cavity. The increase of intra-abdominal pressure (IAP) induced by the PNP and positioning during the procedure may lead to intraoperative hemodynamic instability and respiratory compromise.¹

Carbon dioxide is insufflated into the peritoneal cavity at a rate of 4 to 6 L/min to a pressure of 10 to 14mm of Hg. The PNP is maintained by a constant flow of 200 to 400m1/min. The raised IAP due to PNP, alteration in the patient's positioning and effects of CO₂ absorption induce pathophysiological changes that complicate anaesthetic management.

Large increases in lung and chest wall elastance as well as lung resistance occur with abdominal insufflation of carbon dioxide during laparoscopic surgery. To examine whether these effects were reversible with abdominal deflation, lung and chest wall elastances and resistances were calculated from measurement of airway flow and oesophageal pressure in 17 anesthetized/paralyzed patients undergoing laparoscopic surgery. Measurements were made immediately prior to abdominal insufflation and after deflation. Lung and chest wall elastance and resistance were not changed from baseline (p<0.05), although total respiratory elastance remained slightly increased compared to baseline (p<0.05), the change in total respiratory elastance did not correlate with abdominal insufflation time, surgical site, smoking history, or physical characteristics of the patient. There were no differences in frequency and tidal volume dependences of the elastance and resistance before and after abdominal insufflations (p<0.05). It was concluded that residual changes in respiratory mechanics caused by carbon dioxide insufflation during laparoscopic surgery are minor, and that the reported compromise of respiratory function indicated by pulmonary function tests after laparoscopy does not appear to be due to changes in passive mechanical properties of the lungs or chest wall.¹⁷

A study was conducted to determine whether laparoscopy impairs cardiac performance when preventive measures to improve venous return are taken and to analyze the effects of positioning, anaesthesia and increased intra-abdominal pressure. Using invasive monitoring, hemodynamic changes were investigated in 15 ASA class I or II patients under isoflurane-fentanyl anaesthesia during laparoscopic cholecystectomy. Before laparoscopy, the patients received an intravenous (i.v.) infusion of colloid solution if cardiac filling pressures were low and their legs were wrapped from toes to groin with elastic bandages. Measurements were taken while the patients were awake in the supine (baseline) and head-up tilt (15 to 20 degrees) positions, and after induction of anaesthesia in the same positions. Measurements were repeated at regular intervals during laparoscopy (IAP at 13 to 16mm of Hg), after deflation of the gas and in the recovery room. It was found that with passive head-up tilt in awake and anesthetized patients, the cardiac index (CI), stroke index (SI), central venous pressure (CVP), and pulmonary capillary wedge pressure (PCWP) decreased; and the systemic vascular resistance increased. With the patient under anaesthesia, SI decreased but CI did not change significantly as a result of the compensatory increase in the heart rate. Carbon dioxide insufflation at the start of laparoscopy produced increases in CVP and PCWP as well as mean systemic and mean pulmonary arterial pressures without changes in CI or SI. Towards the end of laparoscopy, CI decreased by l5%. The hemodynamic values returned to nearly pre laparoscopic levels after deflation of the gas, and CI was elevated during the recovery period whereas, systemic vascular resistance was decreased in comparison with the baseline. It was concluded that by correcting relative dehydration and preventing the pooling of blood, CI decreased less than 20% during pneumoperitoneum as compared with the baseline awake levels. The head-up positioning accounts for many of the adverse effects in hemodynamics during laparoscopic cholecystectomy.³

A prospective randomized clinical study was conducted in the Department of Anaesthesiology at Gulbarga Institute Of Medical Sciences  Kalaburagi, The study was carried out on 90 patients belonging to American Society of Anaesthesiology (ASA) classification for physical status I and II of either sex in the age range of 18 to 60 years undergoing laparoscopic procedures under general anaesthesia. They were randomized into two groups of 45 each.

Group D - Dexmedetomidine Group

Group S - Control Group

Inclusion criteria

1. Patients of age between 18 - 60 years
2. ASA Grade I & II patients
3. Type of surgery - elective laparoscopic surgeries
4. Mallampati grade I and II
5. Patients giving valid and informed consent.

Exclusion criteria

1. Patients with anticipated difficult airway
2. Oropharyngeal pathology
3. Patients on beta blockers, patients with conduction defects of the heart (heart blocks)
4. Patients with known allergy to the drug
5. Pregnant women
6. Morbidly obese (body mass index > 35 kg/m²)

PROCEDURE:-

Patients undergoing elective laparoscopic procedures, under general anaesthesia were screened for the eligibility. Patients fulfilling selection criteria were selected for the study and briefed about the nature of study and explained about anesthetic procedure in their vernacular language. A written informed consent was obtained from the patient.

A preanesthetic evaluation with detailed medical history and systemic examination was done and relevant investigations were advised and reviewed on the previous day and on the day of surgery. Patients were randomized into two groups:

• Group D patients received intravenous Dexmedetomidine Perioperatively. (Study group)
• Group S patients received intravenous normal saline 0.9% Perioperatively. (Placebo)

The study drug was provided as prefilled identical lml syringes for the loading dose and 50 ml syringes for the infusion dose containing study drugs, as per the randomization protocol, in dilutions of;

For loading dose:

1. Dexmedetomidine - 1ml (100mcg/ml)
2. Normal saline 0.9% - lml

For infusion:

1. Dexmedetomidine - 50m1 (1mcg/ml)
2. Normal saline 0.9% - 50ml

Patients were explained about the study, but did not know which drug was used. Two intravenous lines were secured, one 20 G intravenous i.v cannula in the right hand for infusion of the study drug and another 18G i.v cannula in the left hand for intravenous fluids and drug administration.

After securing intravenous access, all patients were premedicated with inj. ranitidine 1mg/kg i.v and inj. Ondensetron 0.08mg/kg i.v, 500ml of crystalloids (Ringer Lactate) i.v was started. On arrival in the operation theater baseline monitors like ECG, Pulse-Oximeter and Non - Invasive Blood Pressure (NIBP) were attached. Baseline values of Heart rate (HR), Oxygen Saturation (SPO₂), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) were noted. All patients received inj. Midazolam 0.04mg/kg i.v and inj. Glycopyrrolate 4 micrograms/kg i.v. The study drug was started 20 minutes prior to induction. Patients belonging to group D received a loading dose of dexmedetomidine at 1mcg/kg over 10minutes, followed by maintenance infusion of dexmedetomidine at the rate of 0.4mcg/kg/hr. Patients belonging to the Group S received normal Saline 0.9% at a similar rate as dexmedetomidine infusion.

All patients received inj. Fentanyl l.5mcg/kg i.v 5minutes prior to induction of general anaesthesia. Patients were pre-oxygenated with 100% FiO₂ for 5minutes. General anaesthesia was induced with inj. Propofol 2mg/kg i.v Inj. Succinylcholine 2mg/kg i.v was administered to Facilitate intubation. All patients were intubated with appropriate size cuffed Endotracheal Tubes. End - Tidal Carbon dioxide (ETCO₂) was monitored throughout the surgery and maintained between 35-40 mm of Hg by adjusting the minute ventilation. General anaesthesia was maintained on O₂, N₂O, Isoflurane and inj. Vecuronium bromide 0.08mg/kg. The maximum concentration of Isoflurane used was 1.5% Pneumoperitoneum was created slowly, starting at 2 litre/min, using CO₂ and the Intra Abdominal Pressure (IAP) was maintained between 12-14mm of Hg. Fall in MAP of more than 20% of basal MAP was treated with iv fluids and iv ionotropes. Hemodynamic Parameters including HR, SPO_2, SBP, DBP and MAP were noted.

Statistical Analysis

Data obtained was decoded and entered into a Microsoft excel spreadsheet. The categorical data was expressed in terms of ratios and percentage; and continuous data expressed in terms of mean ± standard deviation. Data analysis was carried out using SPSS v:17 software. Students unpaired "t"/ Mann Whitney U test was used to compare quantitative variables in both groups. The categorical data was compared using chi square test. The probability value (p-value) less than 0.05 (p<0.05) was considered to be statistically significant.

Table 1: Table showing the number of patients in both groups.

GROUP D, n: 45, received inj. Dexmedetomidine i.v., in the perioperative period.

GROUP S, n: 45, received normal saline 0.9%, in the perioperative period.

In group D, maximum number of patients i.e.28 (62.2%) were in the age group of 19-39 years, whereas 22 (49%) were in the age group of 40-60 years. In Group S, maximum number of patients i.e. 23 (51%) were in the age group of 40-60 years, whereas 17 (37.8%) were in the age group of 19-39 years. The mean age of all patients in group D was 37.06±11.56 years while that in group S was 37.77±11.78 (p=0.773, p>0.05). Thus both groups were statistically comparable as far as age was concerned.

The number of females in group D was 19 and in group S was 25. The number of males in group D was 26 and in group S was 20 (P: 0.2058, P>0.05), thus the both groups were comparable statistically as far as sex is concerned.

Table 2: Table showing Mean Weight of patients in both groups.

NS - Not Significant

The mean weight of patients in group D was 66.15±7.05 kg where as in group S it was 66.02±6.12 kg. (P: 0.903, P>0.05), thus the both groups were statistically comparable as far as body weight is concerned.

The number of ASA grade I patients in group D were 32 and in group S were 37.The number of ASA grade II patients in group D was 13 and in group S were 8. Both groups were comparable as far as the ASA grading was concerned as the p value is 0.2127, (p value>0.05).

Graph 1: Graph showing distribution of patients as per ASA classification in both groups.

Table 3: Demographic profile of both the groups.

NS - Not Significant

Graph 2: Graph showing type of surgeries in both groups.

Patients undergoing three types of laparoscopic surgeries were included in the present study- laparoscopic appendectomy, laparoscopic cholecystectomy and laparoscopic umbilical hernia repair. 22(49%) patients in group D and 23(51%) patients in the group S underwent laparoscopic appendectomy. 14(31%) patients in group D and 13(29%) patients in group S underwent Laparoscopic cholecystectomy. 9(20%) patients in group D and 9(20%) patients in group S underwent  laparoscopic umbilical hernia repair. P value was 0.7923 (p>0.05), which indicates that the three groups were comparable in terms of type of surgery the patients underwent.

Table 4: Table showing requirement of intra-operative Nitroglycerine (NTG) drip for control of hypertension in both the group.

S = Significant

Ten out of 45 patients (22%) required intra-operative NTG drip for control of hypertension in group S (placebo), whereas none of the patients in group D required NTG drip. p value was 0.0008 (p<0.05) and thus the difference is statistically significant.

Table 5: Table showing requirement of intraoperative atropine to treat bradycardia in both the groups.

                              S -Significant

Four out of 45 (9%) patients in group D required inj. Atropine for the treatment of bradycardia (HR<50bmp). On the other hand none of the patients in the group S (placebo) required the use of atropine intraoperatively. p value was 0.0408 i.e. p>0.05, thus it is statistically significant.

Table 6: Table showing post-operative nausea vomiting (PONV) in both groups.

NS= Not significant

Six patients out of 45 (13%) of the group D experienced Post-Operative Nausea and Vomiting (PONV), while in Group S (placebo) 7 out of 45 patients (16%) experienced PONV. p value for PONV was 0.7643 which means (p>0.05), thus it is statistically not significant

Laparoscopic surgeries have become the gold standard for many surgical procedures, like laparoscopic cholecystectomy for gall bladder diseases. But laparoscopic surgery requires creation of Pneumoperitoneum by insufflation of carbon dioxide (CO₂) into the peritoneal cavity. Pneumoperitoneum has its own adverse effects due to raised intra-abdominal pressure (IAP), patient positioning and absorption of CO₂, in addition to release of vasopressin and catecholamines. These pathophysiological changes are because of combination of mechanical and neurohumoral factors. These changes are particularly more pronounced in the cardiovascular system. Intraoperative hypertension and tachycardia are the most common hemodynamic disturbances in patients undergoing laparoscopic surgeries.

Many methods have been proposed to attenuate these hemodynamic responses during laparoscopic surgeries. Modifications in surgical techniques have been proposed. Some of them include using abdominal wall lift methods (Laparotensors), use of low pressure pneumoperitoneum, and use of other gases in place or in combination with CO₂ for creation of pneumoperitoneum. Various anaesthetics techniques have also been used. Epidural, segmental spinal anaesthesia and epidural analgesia combined with general anaesthesia have been successfully used to attenuate the hemodynamic responses during laparoscopic procedures. Various drugs like esmolol, nitroglycerine, magnesium sulphate and alpha-2 adrenergic agonists like clonidine and dexmedetomidine have been used with varying degrees of success. Use of high doses of remifentanil almost completely prevents the hemodynamic changes. The alpha-2 adrenoreceptor agonists have several beneficial actions during the perioperative period. They exert a central sympatholytic action, improving hemodynamic stability in response to endotracheal intubation and surgical stress, reducing the anesthetic and opioid requirements and causing sedation, anxiolysis and analgesia.

In group S, out of the 45 patients, 10 (22%) patients required intra-operative drip of inj. Nitroglycerine (NTG) for control of hypertension (defined as an increase of more than 20% in the MAP from the baseline not controlled by an isoflurane concentration of 1.5%). On the other hand none of the patients in group D required a NTG drip.

Direct laryngoscopy and endotracheal intubation following induction of anaesthesia is associated with hemodynamic changes due to reflex sympathetic discharge caused by epipharyngeal and laryngopharyngeal stimulation. This increased sympatho-adrenal activity may result in hypertension, tachycardia and arrhythmias.^4,5

               This increase in blood pressure and heart rate are usually transient, variable and unpredictable. The magnitude of the response is greater with increasing force and duration of laryngoscopy.¹⁵² The elevation in arterial pressure typically starts within five seconds of laryngoscopy, peaks in 14 min and returns to control levels within 5 minutes.

               Dexmedetomidine, being a central sympatholytic, has been used in various doses to attenuate the hemodynamic responses due to laryngoscopy and endotracheal intubation. In our study, we confirmed that dexmedetomidine infusion given 20 minutes prior to induction of general anaesthesia, effectively blunted the reflex tachycardia and hypertension caused due to laryngoscopy and intubation.

Yildiz et al.⁶ evaluated the effect of a single pre-induction i.v. dose of dexmedetomidine 1mcg/kg on the cardiovascular response resulting from laryngoscopy and endotracheal intubation. They found that in the dexmedetomidine group the increase in blood pressure and heart rate after tracheal intubation was significantly lower as compared to the placebo group.

Sulaiman et al.⁷ studied the efficacy of i.v. dexmedetomidine (0.5mcg/kg given 10 minutes prior to induction) for attenuation of cardiovascular responses to laryngoscopy and endotracheal intubation in patients with coronary artery disease. They too found that dexmedetomidine at a dose of 0.5mcg/kg as l0 minute infusion, administered prior to induction of general anaesthesia, attenuates the sympathetic response to laryngoscopy and intubation in patients undergoing myocardial revascularization.

Cho JS et al.⁸ also had similar findings when using i.v. dexmedetomidine pre-treatment in the doses of 0.5mcg/kg or 1.0mcg/kg. Dexmedetomidine suppressed sympathetic hyperactivity and attenuated QTc prolongation during intubation.

Lawrence et al.⁹ found decreased hemodynamic response to tracheal intubation or extubation following a single high dose of dexmedetomidine (2mcg/kg).

Isoflurane requirement was found to be significantly less in Group D as compared to Group S. The requirement of isoflurane was significantly higher in Group S.

Khan ZP et al.¹⁰ studied the effects of dexmedetomidine on isoflurane requirements in healthy volunteers. They concluded that dexmedetomidine decreased isoflurane requirements in a dose dependent manner.

Tufanogullari B et al.¹¹ also found reduced average end-tidal desflurane concentrations with dexmedetomidine infusions.

Ghodki PS et al.¹² in their study found that dexmedetomidine infusion reduced the end-tidal concentration of isoflurane requirement for maintenance of anaesthesia by 30%, while maintaining adequate depth of anaesthesia.

Post-operative nausea and vomiting (PONV):

Post-operative nausea vomiting occurred in 6 out of 45 patients (13%) in group D, whereas it occurred in 7 out of 45 (16%) patients in group S. P value was 0.764 (P >0.05), and thus the difference was statistically not significant.

Our findings did not correlate with the study by Tufanogullari B et al.¹¹ in which 70% of the patients in the placebo group suffered from PONV while only 30% patients in the dex 0.2 and dex 0.4 group suffered from PONV. Only 10% of the patients of the dex 0.8 group suffered from PONV. This may be because all our patients already received inj. Ondensetron and inj. Ranitidine as premedication.

Perioperative intravenous dexmedetomidine as a loading dose of 1mcg/kg/hr over 10mins prior to induction, followed by an infusion of 0.4mcg/kg/hr in ASA I and II patients was found to be effective in providing intraoperative hemodynamic stability during laparoscopic surgeries without any significant adverse effects.

Hence dexmedetomidine can be safely used to attenuate the hemodynamic responses during laparoscopic surgeries with the added advantage of it being an adjuvant to general anaesthesia.

However additional studies are necessary to ascertain the efficacy and safety of dexmedetomidine in elderly and ASA III and IV patients, particularly in those with compromised cardiovascular function.

1. Cunningham A, Brull S. Laparoscopic Cholecystectomy. Anesthesia & Analgesia. 1993;76(5):1120-33.
2. Fahy BG, Barnas GM, Nagle SE, Flowers JL, Njoku MJ, Agarwal M. Changes in lung and chest wall properties with abdominal insufflation of carbon dioxide are immediately reversible. Anesthesia & Analgesia. 1996 Mar 1;82(3):501-5.
3. Hirvonen EA, Poikolainen EO, Pääkkönen ME, Nuutinen LS. The adverse hemodynamic effects of anesthesia, head-up tilt, and carbon dioxide pneumoperitoneum during laparoscopic cholecystectomy. Surgical endoscopy. 2000 Mar 1;14(3):272-7.
4. Stoelting RK. Blood pressure and heart rate changes during short-duration laryngoscopy for tracheal intubation: influence of viscous or intravenous lidocaine. Anesthesia & Analgesia. 1978 Mar 1;57(2):197-9.
5. Prys-Roberts C, Greene L, Meloche R, FoaX P. Studies of anaesthesia in relation to hypertension ii: haemodynamic consequences of induction and endotracheal intubation. Br J Anaesth. 1971;43(6):531-47.
6. Yildiz M, Tavlan A, Tuncer S, Reisli R, Yosunkaya A, Otelcioglu S. Effect of dexmedetomidine on haemodynamic responses to laryngoscopy and intubation. Drugs in R & D. 2006 Jan 1;7(1):43-52.
7. Sulaiman S, Karthekeyan RB, Vakamudi M, Sundar AS, Ravullapalli H, Gandham R. The effects of dexmedetomidine on attenuation of stress response to endotracheal intubation in patients undergoing elective off-pump coronary artery bypass grafting. Annals of cardiac anaesthesia. 2012 Jan 1;15(1):39.
8. Cho I, Kim S, Shin S, Pak H, Yang S, Oh Y. Effects of Dexmedetomidine on Changes in Heart Rate Variability and Hemodynamics During Tracheal Intubation. American Journal of Therapeutics. 2014:7.
9. Lawrence CJ, De Lange S. Effects of a single pre‐operative dexmedetomidine dose on isoflurane requirements and peri‐operative haemodynamic stability. Anaesthesia. 1997 Jul;52(8):736-45.
10. Khan ZP, Munday IT, Jones RM, Thornton C, Mant TG, Amin D. Effects of dexmedetomidine on isoflurane requirements in healthy volunteers. 1: Pharmacodynamic and pharmacokinetic interactions. British journal of anaesthesia. 1999 Sep 1;83(3):372-80.
11. Tufanogullari B, White PF, Peixoto MP, Kianpour D, Lacour T, Griffin J, Skrivanek G, Macaluso A, Shah M, Provost DA. Dexmedetomidine infusion during laparoscopic bariatric surgery: the effect on recovery outcome variables. Anesthesia & Analgesia. 2008 Jun 1;106(6):1741-8.
12. Ghodki PS, Thombre SK, Sardesai SP, Harnagle KD. Dexmedetomidine as an anesthetic adjuvant in laparoscopic surgery: An observational study using entropy monitoring. Journal of anaesthesiology, clinical pharmacology. 2012 Jul;28(3):334.