A Randomized Comparison of Initial Hemodynamic Response Between Three Concentrations of Adrenaline in Lignocaine with Submucosal Infiltration in Septorhinoplasty Patients

ABSTRACT

Objective: To assess the cardiovascular responses induced by different nasal adrenaline-lignocaine mixtures infiltrations protocols for patients undergoing septorhinoplasty under general anesthesia.                                                   

Methods: Our prospective investigation enrolled 212 subjects, aged 26-34 yrs, classified as physical status class I by the American Society of Anesthesiologists (ASAI), of both sexes and scheduled for septorhinoplasty under general endotracheal anesthesia during the period from January 2010 to December 2012, at the King Hussein Hospital, King Hussein Medical Centre, Amman, Jordan. Patients were divided randomly into three groups. Patients in group A (n=70) received nasal sub mucosal infiltration of 10.2 ml of lignocaine 1% (10 mg/ml) with adrenaline 0.0025% (25 mcg/ml). Subjects in group B (n=72) received 10.2 ml of lignocaine 1% with adrenaline 0.00125% (12.5 mcg mg/ml), while subjects in group C (n=70) received 10.2ml of lignocaine 1% with adrenaline 0.000625% (6.25 mcg/ml). Cardiovascular parameters including heart rate, systolic blood pressure and mean arterial pressure were recorded every half minute during the first 5 minutes after nasal infiltration. Inter-group statistical comparisons were performed using ANCOVA and intra-group statistical comparisons were achieved using ANOVA. 

Results: In comparison with baseline readings, heart rate was mostly increased, systolic blood pressure was mostly decreased and mean arterial pressure was mostly reduced significantly (P<0.05) at 60 seconds time interval post infiltration in all three groups.

Conclusions: Local nasal sub mucosal infiltration of different adrenaline concentrations containing lignocaine solutions could increase heart rate and reduce mean arterial pressure during the first five minutes after infiltration.

Key words:General anesthesia, Initial Hemodynamic Response, Septorhinoplasty patients

JRMS September 2013; 20(3): 37-43 / DOI: 10.12816/0001039

Local anesthetics, except cocaine, have a biphasic action on vascular smooth muscle, at low concentration they induce vasoconstriction and at clinical concentration they induce mild vasodilatation without hypotension.⁽⁹⁾ So, cardiovascular modifications in our investigation were due to adrenaline absorption.

Yang et al. demonstrated that the cardiovascular effects of local adrenaline infiltration depend on adrenaline dose, vascularity area, rate of adrenaline systemic absorption and physical condition of the subject.  They showed that adrenaline-lignocaine mixture may lead to temporary and clear hypotension.⁽¹⁾  Nasal site is highly vascularized with fast adrenaline absorption,⁽⁹⁾ for that our cardiovascular effects were recorded starting at 60 seconds time interval in our groups. Beta 2 receptors are very sensitive with induced vasodilatation in the muscles, so MAP was reduced by 60 seconds time interval. Partial stimulation of beta1 receptors had positive chronotropy of the heart. A high heart rate was the baroreceptor reflex to a decreased blood pressure. The MAP came back soon reaching a higher number due to the action of beta1 receptor and activation of alpha receptors. The reduction of MAP in our investigation was less than in Yang et al. study (17.7% and 28%, respectively), while the increase in heart rate in our study was 17.5%.⁽¹⁾  Nevertheless, in another study by Yang,⁽⁷⁾ they reported a 20% decrease in MAP and a 15% increase in HR. In a previous study, it was clearly demonstrated that an increased plasma adrenaline concentration occurred during the first 4 minutes after infiltration.⁽¹⁰⁾  Decreased MAP readings signify that cardiovascular modifications of absorbed adrenaline are dose dependent. Adrenaline plasma concentration via a vascular route is significantly less than after surgical stimulation or psychological stress.⁽⁸⁾ General anesthesia decreases the release of endogenous catecholamine, so the modifications in adrenaline blood concentration relative to endogenous adrenaline are low.  General anesthesia covered the symathomimetic action of the total catecholamine in blood. General anesthesia can reduce bleeding, make surgery easier and enhance clarity of surgical field.⁽¹¹⁾

Hypotension after local adrenaline infiltration during the first 5 minutes doesn’t need intervention because soon blood concentration of adrenaline will be adequate. Moshaver et al. demonstrated that following adrenaline injection, increases in the heart rate of 10.2 and 7.4bpm  were noted after one and two minutes in 1/100000 adrenaline concentration compared with 1/200000 adrenaline concentration.  Similarly, systolic pressure had an estimated increase of 17.5mmHg more in 1/100000 group compared with 1/200000 group after one minute and the increase of 18.8mmHg after 2min.⁽²⁾ Yang et al. found that MAP decreased and HR increased at 1.5 min time interval in both previous concentrations.⁽⁷⁾

 Under general anesthesia, 20% of patients breathing 1.25 MAC of halothane and who receive subcutaneous infiltration of 2mcg/kg of adrenaline will exhibit arrhythmias. These increases to 100% of patients receiving 2.5-3mcg/kg. Patients breathing 1.25 MAC of isoflurane or sevoflurane and who receive infiltration of 2mcg/kg of adrenaline will have 0% arrhythmias. For that there was a protocol for the use of adrenaline infiltration with halothane:  Avoid concentrations of adrenaline greater than 1/100000 and avoid a dosage in adults exceeding 10ml of 1/100000 adrenaline in 10 minutes (100mcg) or 30 ml/h (300mcg). Under general anesthesia, at 1.5 MAC, isoflurane produces around 120 bpm with MAP around 60mmHg, sevoflurane produces around stable low or 100bpm  with MAP around 60 mmHg but halothane produces MAP around 70mmHg with low heart rate.⁽⁴⁾  When halothane was used, no patient developed arrhythmias when less than 1.8 mcg/kg was used, but with isoflurane, no arrhythmias occurred when less than 5.4 mcg/kg was used.⁽³⁾

There are few limitations in our investigation. Firstly, it was impossible to evaluate these cardiovascular effects with myocardial inhibition due to general anesthesia. Secondly, our cardiovascular parameters follow-up was only for five minutes and thirdly, we did not measure the plasma concentrations of adrenaline. In the contrary and in favor of our study, deep general anesthesia was maintained before infiltration and local adrenaline infiltration was achieved 15 minutes after orotracheal intubation.

The cardiovascular changes noticed after sub mucosal adrenaline infiltration can be prevented using as low concentration as possible. This can prevent more cardiac adverse events in susceptible subjects and safer surgical conditions Horrigan et al. showed that adrenaline injection even in therapeutic doses can induce increased heart rate with arrhythmias in susceptible patients, with the frequency of hemodynamic toxic side effects increasing in a dose dependent manner.⁽³⁾ A significant increase in the plasma catecholamine level was shown after injection with associated cardiovascular changes due to systemic absorption of adrenaline.⁽¹²⁾

Preventing cardiovascular changes is the essential corner in preventing cardiovascular adverse events. Associated hemodynamic changes during 4mg adrenaline/20 ml saline and 1mg adrenaline/20 ml saline, can be controlled in both groups without significant clinical consequences. The rescue medication need to treat hypertension was more in 1mg adrenaline group but within the recommended limits.⁽¹³⁾

A previous study showed that there was a trend towards elevation of blood pressure in the groups using adrenaline 1/2000 and 1/10000 with a greater occurrence of hypertensive peaks but not using 1/50000. The blood pressure elevation was progressive but very slow during the procedure which could be associated with the anesthesia technique.⁽¹⁴⁾ 

Adrenaline has become popular because it is cheap and available in every hospital. The major difficulty with adrenaline is to establish the dose that provides the best safety and efficacy. There is no standard concentration defined in the medical literature. Furthermore, when applying adrenaline topically, the total amount that is used is hard to establish. Adrenaline concentrations have varied widely in the literature ranging from 1/200000 to 1/50000 for infiltration. The idea that higher concentrations of adrenaline are needed for improved operability has subtly gained strength. This has been due mostly to the protocols used in health care centers with more experience which adopt concentrations for topical use of 1/5000, 1/2000 or 1/1000. Although there has been a world trend to use more concentrated solutions, studies demonstrating improved safety (incidence of systemic effects) with these concentrations, compared to lower concentrations are lacking.⁽¹⁴⁾

At 60 seconds time interval, if we divide the decrease in SBP by the mean duration of adrenaline infiltration (50 sec), the result in group A is 0.3mmHg for each 10 sec of infiltration use, in group B is 0.28mmHg and in group C is 0.26mmHg. If we divide the increase in heart rate by the mean duration of adrenalin infiltration, the result in group A is 0.32bpm for each 10 sec of infiltration use, in group B is 0.28bpm and in group C is 0.24bpm. If we divide the decrease in MAP by the mean duration of adrenaline infiltration (50 sec), the result in group A was 0.3mmHg for each 10 sec of infiltration use, in group B is 0.28 mmHg and in group C is 0.26mmHg.

In our search in literature, we did  find some investigations of adrenaline infiltrations during septorhinoplasy.⁽¹⁵⁾ For that, we related our investigations to nasal surgery, mainly functional endoscopic sinus surgery.  To our surprise, we found that males occupied the largest group (almost double) of our study time during the investigation, but at the same time we did not investigate whether gender had an influence on adrenaline infiltration hemodynamics. We hope that we could study this in the future. 

Conclusion

Cardiovascular modifications were secondary to absorption of adrenaline-lignocaine solution. Local adrenaline infiltration induces cardiovascular modifications of HR and MAP during septorhinoplasty under general anesthesia during the first five minutes after infiltration. At 60 sec time interval after beginning of infiltration, MAP decreased significantly and HR increased significantly. Adrenaline 0.0025% can assist in good surgical field without significant hemodynamic changes or arrhythmias.

References

1.Yang JJ, Li WY, Jil Q, et al. Local anesthesia for functional endoscopic sinus surgery employing small volumes of epinephrine-containing solutions of lidocaine produces profound hypotension. Acta Anesthesiol Scand 2005; 49:1471-1476.

2.Moshaver A, Denny L, Ruxandra P, et al. The hemostatic and hemodynamic effects of epinephrine during endoscopic sinus surgery. Arch Otolaryngology Head Neck Surgery 2009; 135(10):1005-1009.

3. Horrigan RW, Eger EL, Wilson C.  Epinephrine induced arrhythmias during enflurane anesthesia in man: a nonlinear dose response relationship and dose dependent protection from lidocaine. Anesth Analg 1978; 57(5):547-550.       

4.Aitkenhead AR, Smith G, Rowbotham DJ. Inhalational anesthetic agents. In: Parkinson M, Simmons B, editors, Textbook of anesthesia. Netherlands: Churchill livingstone; 2007; 13-33.

5.Mcclymont LG, Crowther JA. Local anesthetic with vasoconstrictor combinations in septal surgery. J laryngol otol 1988; 102(9):793-795.   

6.Cohen-Kerem R, Brown SV, Illasenor LV, et al. Epinephrine /lidocaine injection vs. saline during endoscopic sinus surgery. Laryngoscope 2008; 118(7):1275-1281

7.Yang JJ, Zhenq J, Liu HJ, et al. Epinephrine infiltration on nasal field causes significant hemodynamic changes: Hypotension episode monitored by impedance cardiograph under general anesthesia. J Pharm Pharmaceut Sci 2006; 9(2): 190-197.

8.Moss J, Glick D. The autonomic nervous system. In: Miller RD, editor. Millers anesthesia. New York: Churchill Livingstone; 2005; 617-78.  

9.Pateromichelakis S, Rood JP. Effects of lignocaine on adrenaline induced vasoconstriction. BJA 1986; 58: 649-52. 

10.John G, Low JM, Tan PE, et al. Plasma catecholamine levels during functional endoscopic sinus surgery.Clin Otolaryngol 1995; 20:213-215.

11.Titelli  G,  Bigarini  S,  Russolo  M,  et  al.  Total intravenous anesthesia in endoscopic sinus nasal surgery. Acta Otorhinolaryngol Ital 2004; 24:137-44.  

12.Anderhuber W, Walch C, Nemeth E, et al. Plasma adrenaline concentrations during functional endoscopic sinus surgery. Laryngoscope 1999; 109(2):204-207. 

13.Panda N, Verma RK, Panda NK. Efficacy and safety of high concentration adrenaline wicks during FESS. J Otolaryngol Head Neck Surg 2012; 41(2): 131-137.

14.Sarmento Junior KM, Tomita S, Kos AO. Topical use of adrenaline in different concentrations for FESS. Rev Bras Otorrinolaringol 2009; 75(2): 280-289.

15.Tatjana G, Irena P, Domag P, et al.  The effect  of injection speed on hemodynamic changes immediate after lidocaine / adrenaline infiltration of  nasal  submucosa  under  general  anesthesia. Periodicum   Biologorum  2011;  113 (2):  217-21.