Effect of Retroperitoneal Lavage with Normal Saline Containing Adrenaline on Carbon Dioxide Absorption in Patients Undergoing Retroperitoneal Laparoscopic Surgery

Abstract

Objective:

To determine the effect of lavage with adrenaline solution on CO₂ absorption during retroperitoneal laparoscopic surgery.

Materials and Methods:

Sixty patients scheduled to undergo retroperitoneal laparoscopic surgery were divided into an AD group (lavage with normal saline containing adrenaline [1:500,000], n = 30) and an NS group (lavage with normal saline only, n = 30). After the establishment of artificial pneumoperitoneum and before the start of the operation, the retroperitoneal space was irrigated with 300 mL of normal saline with or without adrenaline, depending on the group. The lavage fluid was aspirated after 3 minutes. Heart rate (HR), mean arterial pressure (MAP), blood oxygen saturation (SpO₂), partial pressure of O₂ (PaO₂), partial pressure of CO₂ (PaCO₂), and end-tidal CO₂ partial pressure (P_ETCO₂) were recorded before the lavage (T₀) and at 10, 30, 60, 90, and 120 minutes (T₁–T₅, respectively) after the lavage. The CO₂ output (VCO₂) was calculated, and the incidence of intraoperative arrhythmia and postoperative complications (e.g., headache, palpitations, irritation) was determined.

Results:

HR, MAP, SpO₂, PaO₂, PaCO₂, P_ETCO₂, and VCO₂ at T₀ did not significantly differ between the groups (P > .05). HR, PaCO₂, P_ETCO₂, and VCO₂ at T₁–T₅ were lower in the AD group than in the NS group (P < .05). The incidence of intraoperative arrhythmia and postoperative complications was lower in the AD group than in the NS group (P < .05).

Conclusions:

Lavage with normal saline containing adrenaline (1:500,000) reduced CO₂ absorption during retroperitoneal laparoscopic surgery, prevented hypercapnia, and decreased intra- and postoperative complications.

Introduction

Retroperitoneal laparoscopic surgery involves the establishment of a lacuna in the retroperitoneal space, which contains the urinary organs. Thus, these organs can be directly operated on via this surgical approach. Retroperitoneal laparoscopic surgery has greatly improved the treatment of urological conditions, as this surgery is associated with minimal injury and pain, rapid recovery, and minimal tumor spread.¹ However, many clinical trials^2,3 have indicated that the incidence of severe hypercapnia is higher after retroperitoneal laparoscopic surgery than after conventional laparoscopic surgery, which suggests that the carbon dioxide absorption rate is higher in the retroperitoneal space than in the abdominal cavity. Hypercapnia can lead to physical dysfunction and even prove life-threatening in perioperative patients, especially elderly patients.^4,5 Therefore, it is necessary to develop safe and effective prevention measures.

Adrenaline, a major neurotransmitter in the adrenal medulla, strongly stimulates alpha and beta receptors and mainly affects the small arteries and precapillary sphincters. Alpha receptors are predominant in the vascular smooth muscles in organs such as the skin, kidneys, and gastrointestinal tract. The strongest vasoconstriction in response to adrenaline stimulation is observed in the skin and mucosa. The visceral vessels, especially the vessels in the kidneys, also exhibit considerable constriction. Owing to this vasoconstrictive effect, adrenaline at concentrations from 1:200,000 to 1:500,000 is commonly used in clinical practice. Local adrenaline administration during surgery can prompt local vasoconstriction, greatly reduce the oozing of blood from the surgical site, and facilitate the achievement of hemostasis with gauze compression.⁶

This study explored the effects of retroperitoneal lavage with normal saline containing adrenaline on carbon dioxide absorption during retroperitoneal laparoscopic surgery. We aimed to determine if the use of this lavage reduced carbon dioxide absorption and prevented the occurrence of severe hypercapnia and its consequences.

Materials and Methods

General information

This clinical study was approved by the ethics committee of our hospital. This study involved a total of 60 patients, 20–65 years of age, weighing 50–90 kg, and with American Society of Anesthesiologists grades of I–II, who were scheduled to undergo elective laparoscopic urologic surgery. The inclusion criteria were as follows: no heart, liver, lung, or kidney dysfunction; operating time greater than 1.5 hours but no more than 4 hours; preoperative blood pressure and blood sugar within the normal range; and operations performed by the same leading surgeon. The exclusion criteria were as follows: hypertension, tachycardia, or coronary heart disease; intraoperative conversion to laparotomy; duration of pneumoperitoneum less than 1 hour or more than 4 hours; obviously abnormal lung function; inadvertent intraoperative peritoneal damage caused by the surgeon; intraoperative pleural damage leading to pneumothorax; severe intraoperative subcutaneous emphysema; severe intraoperative arrhythmia; and patient dependence on alcohol or opiates. The patients were divided into two groups via the random number table method: patients in the AD group underwent retroperitoneal lavage with normal saline containing adrenaline at a concentration of 1:500,000, whereas those in the NS group underwent retroperitoneal lavage with normal saline only (30 patients per group).

Anesthesia

All patients were instructed not to eat or drink for 12 hours before the operation. A peripheral intravenous line was established in the operating room. Patients were routinely administered oxygen and underwent regular electrocardiographic, heart rate (HR), and blood oxygen saturation (SpO₂) monitoring. The radial artery was punctured with a 20-gauge needle and catheterized for continuous invasive monitoring of the mean arterial pressure (MAP); arterial blood was extracted for gas analysis. For anesthesia induction, patients were administered midazolam (0.1–0.5 mg/kg, iv), sufentanil (0.4–0.6 μg/kg, iv), rocuronium (0.6–1.0 mg/kg, iv), and etomidate (0.15–0.3 mg/kg, iv). After anesthesia induction, endotracheal intubation and mechanical ventilation were performed. The respiratory parameters were set as follows: tidal volume ventilation, 8 mL/kg; breathing frequency, 12 times/minute; inspiratory/expiratory time ratio, 1:2; and fraction of inspired oxygen, 80%. Propofol at a rate of 1–2 mg/kg/hour, remifentanil at a rate of 2–4 μg/kg/hour, and cisatracurium besylate at a rate of 0.06–0.12 mg/kg/hour were intravenously infused to maintain anesthesia. Intraoperative hemodynamic stability was achieved, with fluctuations of no more than 20% of the baseline values.

Pneumoperitoneum

After anesthesia induction, the patients were placed in a lateral position, and a 2-cm-long incision was made on the iliac crest in the midaxillary line on the affected side. The dissection was continued up to the lumbar dorsal fascia, and a monohydrate capsule was inserted. Then, 600–800 mL of normal saline (0.9% NaCl) was injected over approximately 5 minutes to distend the lumbar dorsal fascia, and an artificial peritoneal lacuna was established. Next, carbon dioxide pneumoperitoneum was achieved. The carbon dioxide perfusion pressure ranged from 13 to 15 cm of H₂O during the operation.

Preparation of adrenaline solution

The adrenaline mother solution had a concentration of 1 mg/mL, which means that 1 mL of the solution contained 1 mg of adrenaline. Thus, 1000 mL contained 1 g of adrenaline (dilution, 1:1000). We added normal saline to 1 mL of adrenaline mother solution until a volume of 100 mL was reached. We thus obtained an adrenaline solution with a dilution ratio of 1:100,000. Next, normal saline was added to 1 mL of the dilute solution until a volume of 500 mL was reached, yielding an adrenaline solution with a dilution ratio of 1:500,000.

Retroperitoneal lavage

The absence of hemorrhage in the retroperitoneal space was ascertained at the start of the surgery, and artificial pneumoperitoneum was established. Under laparoscopic guidance, 300 mL of the prepared adrenaline solution (1:500,000) was injected into the retroperitoneal space in the AD group, whereas 300 mL of normal saline (0.9% NaCl) was injected in the NS group. The lavage fluid was aspirated after 3 minutes. The vasoactive agents including esmolol hydrochloride injection (Qilu Pharmaceutical Co., Ltd., Jinan, China), nicardipine hydrochloride injection (Astellas Pharma Inc., Tokyo, Japan), atropine sulfate injection (Anyang Jiuzhou Pharmaceutical Co., Ltd., Anyang, China), and adrenaline hydrochloride injection (Tianjin Pharmaceuticals Group Co., Ltd., Tianjin, China), etc., were prepared for avoiding cardiovascular adverse events such as severe alterations in HR or MAP. Severe high or low blood pressure was treated in a timely manner, to avoid serious complications.

Indexes evaluated

The following general information of the patients was recorded: age, gender ratio, body mass index, preoperative pulmonary function, arterial blood gas analysis, and duration of operation. HR, MAP, SpO₂, partial pressure of O₂ (PaO₂), partial pressure of CO₂ (PaCO₂), and end-tidal CO₂partial pressure (P_ETCO₂) were recorded before the lavage (T₀) and at 10 minutes (T₁), 30 minutes (T₂), 60 minutes (T₃), 90 minutes (T₄), and 120 minutes (T₅) after the lavage. The CO₂output (VCO₂) was calculated using the formula given below⁷: \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} \begin{align*}{ \rm VCO}_2 = ( { \rm expiratory \ PaCO}_2 / [ P_{ \rm B} - P_{{ \rm H}2{ \rm O}} ] ) \times V_{ \rm T} \times RR\end{align*} \end{document}

where V_T is the tidal volume, RR is the ratio of respiration, P_B is the atmospheric pressure (760 mm Hg), and P_H2O is the vapor pressure of saturated water at 37°C (47 mm Hg; 1 mm Hg = 0.133 kPa). The incidence rates of intraoperative arrhythmia and postoperative complications such as headache, palpitations, and irritation were also determined.

Statistical analysis

Statistical analysis was performed using SPSS version 15.0 statistical software (SPSS, Inc., Chicago, IL). Measurement data were expressed as mean ± standard deviation values. The two-samples t test was used for comparisons between the two groups, and one-way analysis of variance was used for comparisons of indexes between different time points in each group. The chi-squared test was used to compare count data. P values of < .05 were considered to indicate statistically significant differences.

Results

There was no significant difference in age, gender ratio, body mass index, preoperative pulmonary function, arterial blood gas analysis, and duration of operation between the two groups (P > .05) (Table 1).

Table 1.

Comparison of General Indexes Between the Two Groups

Index	AD group	NS group	P value
Age (years)	50 ± 8	51 ± 7	.608
Sex (male/female) (n)	22/8	20/10	1.000
BMI (kg/m²)	21.0 ± 2.5	20.3 ± 2.4	.273
ASA classification (I/II) (n)	9/21	8/22	1.000
pH value	7.38 ± 0.04	7.40 ± 0.05	.692
PaO₂ (mm Hg)	79.8 ± 12.3	80.8 ± 9.9	.730
PaCO₂ (mm Hg)	39.7 ± 3.9	40.9 ± 3.4	.495
Hemoglobin (g/L)	117.6 ± 11.3	114.5 ± 13.8	.330
FEV₁ (%)	80 ± 9	78 ± 12	.468
FVC (%)	86 ± 12	84 ± 14	.555
FEV₁/FVC (%)	81 ± 12	79 ± 13	.538
Surgical time (minutes)	186 ± 13	184 ± 15	.583

Data are mean ± standard deviation values unless indicated otherwise (n = 30).

AD group, lavage with normal saline containing adrenaline (1:500,000) group; ASA, American Society of Anesthesiologists; BMI, body mass index; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; NS group, lavage with normal saline only group; PaCO₂, partial pressure of CO₂; PaO₂, partial pressure of O₂.

In addition, there was no significant difference in HR, MAP, SpO₂, and PaO₂ at T₀ and in SpO₂ and PaO₂ at T₁–T₅ between the two groups (P > .05). In the NS group, HR was higher at T₁–T₅ than at T₀ (P < .05). The HR at T₁–T₅ was lower in the AD group than in the NS group (P < .05). There was no significant difference in MAP at the different time points between the two groups (P > .05) (Table 2).

Table 2.

Comparison of Heart Rate, Mean Arterial Pressure, Oxygen Saturation, and Partial Pressure of O₂ at Different Time Points Between the Two Groups

	Timing
Index, group	T₀	T₁	T₂	T₃	T₄	T₅
HR (beats/minute)
AD group	80 ± 8	75.7 ± 11.3^a,b	80.8 ± 15.7^a,b	81.5 ± 18.7^a,b	83.7 ± 16.6^a,b	85.6 ± 15.6^a,b
NS group	78 ± 7	89.8 ± 13.9	95.7 ± 19.8	98.5 ± 17.8	97.6 ± 15.6	97.5 ± 14.7
t value	1.09	6.89	7.62	7.90	6.43	6.31
P value	.608	<.001	<.001	<.001	<.001	<.001
MAP (mm Hg)
AD group	80.7 ± 12.4	72.9 ± 18.1	81.7 ± 19.4	77.7 ± 18.6	79.6 ± 20.3	81.4 ± 16.5
NS group	82.3 ± 11.2	71.5 ± 19.7	82.5 ± 17.7	78.4 ± 15.7	79.5 ± 17.6	81.5 ± 18.6
t value	0.98	1.29	1.25	1.25	0.97	0.89
P value	.891	.432	.623	.556	.574	.352
SpO₂ (%)
AD group	99.5 ± 0.4	99.2 ± 0.5	98.7 ± 0.7	99.2 ± 0.6	98.5 ± 0.6	99.3 ± 0.7
NS group	99.6 ± 0.3	98.5 ± 0.8	99.2 ± 0.4	99.1 ± 0.6	99.0 ± 0.7	98.9 ± 0.7
t value	0.87	1.12	1.05	1.01	0.95	0.86
P value	.770	.636	.753	.863	.545	.694
PaO₂ (mm Hg)
AD group	312.9 ± 77.5	352.8 ± 53.3	325.5 ± 65.8	329.6 ± 78.3	379.8 ± 79.8	315.7 ± 96.7
NS group	342.6 ± 69.9	364.7 ± 42.5	322.3 ± 45.9	324.6 ± 98.4	378.4 ± 72.6	324.5 ± 82.4
t value	0.86	1.31	1.05	1.05	0.96	0.75
P value	.783	.458	.572	.578	.631	.642

Data are mean ± standard deviation values (n = 30).

P < .05 versus before lavage (T₀) in the same group; ^bP < .05 versus the lavage with normal saline only (NS) group.

AD group, lavage with normal saline containing adrenaline (1:500,000) group; HR, heart rate; MAP, mean arterial pressure; SpO₂, blood oxygen saturation; PaO₂, partial pressure of O₂; T₁–T₅, 10, 30, 60, 90, and 120 minutes, respectively, after the lavage.

There was no significant difference in PaCO₂, P_ETCO₂, and VCO₂ at T₀ between the two groups (P > .05). In both groups, PaCO₂, P_ETCO₂, and VCO₂ were higher at T₁–T₅ than at T₀ (P < .05). PaCO₂, P_ETCO₂, and VCO₂ at T₁–T₅ were significantly lower in the AD group than in the NS group (P < .05) (Table 3).

Table 3.

Comparison of Partial Pressure of CO₂, End-Tidal CO₂ Partial Pressure, and CO₂ Output at Different Time Points Between the Two Groups

	Timing
Index, group	T₀	T₁	T₂	T₃	T₄	T₅
PaCO₂ (mm Hg)
AD group	35.7 ± 3.9	37.5 ± 5.5^a,b	38.5 ± 4.7^a,b	40.3 ± 4.0^a,b	42.0 ± 5.2^a,b	42.8 ± 4.9^a,b
NS group	34.9 ± 3.4	39.6 ± 4.8	42.2 ± 5.6	46.0 ± 5.2	47.0 ± 4.8	48.9 ± 4.9
t value	1.84	6.79	7.67	8.63	6.98	7.56
P value	.401	<.001	<.001	<.001	<.001	<.001
P_ETCO₂ (mm Hg)
AD group	33.6 ± 5.1	33.5 ± 3.5^a,b	34.5 ± 3.0^a,b	36.2 ± 5.1^a,b	37.9 ± 5.3^a,b	38.5 ± 6.0^a,b
NS group	33.5 ± 6.0	36.1 ± 3.6	38.5 ± 3.9	41.8 ± 4.7	43.4 ± 4.4	45.9 ± 6.9
t value	0.96	6.99	7.69	8.89	6.88	7.89
P value	.678	<.001	<.001	<.001	<.001	<.001
VCO₂ (mL/minute)
AD group	130 ± 29	145.5 ± 12.7^a,b	151.6 ± 21.4^a,b	171.5 ± 20.6^a,b	175.6 ± 22.4^a,b	177.5 ± 24.6^a,b
NS group	132 ± 33	166.7 ± 17.3	180.4 ± 19.4	199.6 ± 41.3	206.3 ± 38.6	215.4 ± 41.7
t value	1.53	16.8	18.6	17.8	16.7	17.4
P value	.365	<.001	<.001	<.001	<.001	<.001

Data are mean ± standard deviation values (n = 30).

P < .05 versus before lavage (T₀) in the same group; ^bP < .05 versus the lavage with normal saline only (NS) group.

AD group, lavage with normal saline containing adrenaline (1:500,000) group; PaCO₂, partial pressure of CO₂; P_ETCO₂, end-tidal CO₂ partial pressure; T₁–T₅, 10, 30, 60, 90, and 120 minutes, respectively, after the lavage; VCO₂, CO₂ output.

The incidence rates of intraoperative arrhythmia and postoperative complications such as headache, palpitations, and irritation were significantly lower in the AD group than in the NS group (P > .05) (Table 4).

Table 4.

Comparison of the Incidence of Intra- and Postoperative Adverse Reactions (n = 30)

Index	AD group	NS group	χ ² value	P value
Headache	2 (6.7%)^a	5 (16.7%)	6.90	<.001
Palpitation	1 (3.3%)^a	3 (10%)	5.76	.016
Irritation	1 (3.3%)^a	4 (13.3%)	6.77	<.01
Atrial premature beat	0 (0%)^a	1 (3.3%)	7.93	.032
Premature ventricular contraction	1 (3.3%)^a	4 (13.3%)	8.78	<.001
Atrial fibrillation	0 (0%)^a	1 (3.3%)	4.32	.024

P < .05 versus the lavage with normal saline only (NS) group.

AD group, lavage with normal saline containing adrenaline (1:500,000) group.

Discussion

Acute myocardial damage is one of the main complications induced by hypercapnia and can decrease cardiac contractility. Carbon dioxide directly inhibits myocardial contraction and smooth muscle contraction, leading to the dilation of small arteries.⁸ Additionally, increased PaCO₂ can indirectly stimulate the sympathetic nervous system to cause catecholamine release, which increases HR, cardiac output, and blood pressure and thereby increases cardiac preload and afterload, as well as myocardial oxygen consumption. Furthermore, the diastolic period is shortened, and coronary blood supply is reduced, which worsens the myocardial ischemia and increases the risk of arrhythmia, heart failure, and other severe adverse consequences.⁹ Acidosis causes a stress response, which results in failure of the microcirculation and can lead to the occurrence of systemic inflammatory response syndrome followed by multiple organ dysfunction.¹⁰ In addition, the intraoperative systemic vasodilation in response to hypercapnia, which includes cerebrovascular dilation, can cause adverse reactions such as headache, nausea, and irritability.¹¹

Adrenaline exhibits dose-dependent effects on the cardiovascular system, and at doses exceeding 10 μg/minute, it mainly stimulates the alpha receptors, causing vasoconstriction.¹² The concentration of adrenaline used for local infiltration anesthesia ranges from 1:200,000 to 1:500,000. At these concentrations, the vasoconstrictive effect of adrenaline is exclusively local, and excessive absorption of adrenaline into the circulation, which can lead to hypertension and tachycardia, is avoided. The lowest adrenaline concentration used in local infiltration anesthesia is 1:500,000.¹³ At this concentration, the onset of peripheral vasoconstriction occurs at 3–6 minutes and lasts for 2–4 hours. The effect is moderate, and thus local ischemic injury can be avoided. The retroperitoneal space contains abundant loose connective tissue. Therefore, adrenaline absorption is lower after retroperitoneal lavage than after local infiltration, and the influence on hemodynamics can be minimized.

In this study, normal saline containing adrenaline at a concentration of 1:500,000 was used to reduce intraoperative carbon dioxide absorption, decrease the incidence of hypercapnia, and keep the intra- and postoperative hemodynamics stable in patients undergoing retroperitoneal laparoscopic surgery. The main factors influencing carbon dioxide levels included the metabolic rate of carbon dioxide production, the amount of carbon dioxide in the blood, and the expiratory carbon dioxide level. The blood carbon dioxide level paralleled PaCO₂, and the expiratory carbon dioxide level paralleled P_ETCO₂. We found that PaCO₂, P_ETCO₂, and VCO₂ at T₁–T₅ were lower in the AD group than in the NS group, which indicates that lavage with the adrenaline solution reduced carbon dioxide absorption and decreased the incidence of hypercapnia. In addition, the incidence of adverse reactions caused by hypercapnia such as intraoperative tachycardia and arrhythmia and postoperative headache, palpitation, and irritability was lower in the AD group than in the NS group. Thus, the retroperitoneal lavage improved surgical safety and decreased the incidence of adverse events. This technique may be used to prevent hypercapnia in patients undergoing retroperitoneal laparoscopic surgery.

The advantages of retroperitoneal lavage with adrenaline solution do not apply to retroperitoneal laparoscopic surgery of long duration (>4 hours), and this method cannot be used in patients with extensive subcutaneous emphysema. In addition, incorrect application of the lavage technique may lead to excessive adrenaline absorption into the circulation, causing serious consequences. Therefore, the next target of this study is to search for some simpler and more feasible prevention measures.

In conclusion, retroperitoneal lavage with normal saline containing adrenaline at a concentration of 1:500,000 reduced carbon dioxide absorption during retroperitoneal laparoscopic surgery and prevented the occurrence of hypercapnia, thereby decreasing the incidence of intra- and postoperative complications.

Footnotes

Acknowledgments

We thank Jia-Qiang Zhang and De-Gang Ding for excellent technical assistance.

Disclosure Statement

No competing financial interests exist.

References

Petrucciani

, Sirimarco

, Magistri

, et al. Retroperitoneal schwannomas: Advantages of laparoscopic resection. Review of the literature and case presentation of a large paracaval benign schwannoma (with video). Asian J Endosc Surg, 2015; 8:78–82.

Streich

, Decailliot

, Perney

, et al. Increased carbon dioxide absorption during retroperitoneal laparoscopy. Br J Anaesth, 2003; 91:793–796.

Wolf

Jr , Monk

, McDougall

, et al. The extraperitoneal approach and subcutaneous emphysema are associated with greater absorption of carbon dioxide during laparoscopic renal surgery. J Urol, 1995; 154:959–963.

Atallah

, Bastide-Heulin

, Soulié

, et al. Haemodynamic changes during retroperitoneoscopic adrenalectomy for phaeochromocytoma. Br J Anaesth, 2001; 86:731–733.

Catani

, Guerricchio

, De Milito

, et al. “Low-pressure” laparoscopic cholecystectomy in high risk patients (ASA Ill and IV): Our experience [in Italian]. Chir Ital, 2004; 56:71–80.

Ogbemudia

, Bafor

, West-Osemwengie

. Reactionary haemorrhage reduction with adrenaline infiltration in proximal tibial osteotomy: A randomized clinical study of safety and efficacy. Arch Orthop Trauma Surg, 2012; 132:21–24.

, Gill

, Sung

, et al. Retroperitoneoscopic surgery is not associated with increased carbon dioxide absorption. J Urol, 1999; 162:1268–1272.

Falabella

, Moore-Jeffries

, Sullivan

, et al. Cardiac function during steep Trendelenburg position and CO₂ pneumoperitoneum for robotic-assisted prostatectomy: A trans-oesophageal Doppler probe study. Int J Med Robot, 2007; 3:312–315.

Andersson

, Jogestrand

, Thörne

, et al. Are there changes in leg vascular resistance during laparoscopic cholecystectomy with CO₂ pneumoperitoneum?. Acta Anaesthesiol Seand, 2005; 49:360–365.

10.

Komori

, Takada

, Tomizawa

, et al. Permissive range of hypercapnia for improved peripheral microcirculation and cardiac output in rabbits. Crit Care Med, 2007; 35:2171–2175.

11.

Lee

, Lee

, Do

, et al. The effect of gynaecological laparoscopic surgery on cerebral oxygenation. J Int Med Res, 2006; 34:531–536.

12.

Moss

, Renz

. The autonomic nervous system. In: Miller RD: Anesthesia, 5th ed. New York: Churchill Livingstone, 2000, pp. 523–577.

13.

Grabb

. A concentration of 1:500000 epinephrine in a local anesthetic solution is sufficient to provide excellent hemostasis. Plast Reconstr Surg, 1979; 63:834.