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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 3  |  Issue : 4  |  Page : 157-162

Conivaptan prophylactically in transurethral resection of prostate surgeries


Department of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission09-Jun-2016
Date of Acceptance22-Oct-2016
Date of Web Publication16-Dec-2016

Correspondence Address:
Ahmed Nabil Ibrahim
Department of Anesthesia, Intensive Care and Pain Management, Faculty of Medicine, Ain Shams University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2356-9115.195879

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  Abstract 

Background
Transurethral resection of prostate (TURP) requires the use of irrigating fluids. The absorption of large volumes of these fluids may lead to hyponatremia and consequently TURP syndrome. If not treated promptly, the patient becomes cyanotic, hypotensive, and ultimately sustains cardiac arrest. Conivaptan is one of vaptans, a new group of vasopressin receptor antagonists that are increasingly being used for the treatment of euvolemic, hypervolemic forms of hyponatremia especially in the ICU.
This study evaluates the efficacy of a single dose of conivaptan to prevent hyponatremia in TURP patients.
Patients and methods
In a prospective, randomized, double-blinded study, 50 male patients scheduled for elective TURP under central neuraxial block were included in this study. Patients were divided into two groups (A and B) (n=25 for each group). Group A patients received intravenous conivaptan 20 mg over 30 min, whereas group B was the control group who received the usual maintenance fluid. Preoperative serum sodium and potassium levels in patients were measured, followed by intraoperative levels, and these levels were recorded after 60 min by blood gas analyzer using venous blood samples. All patients were carefully observed for the early symptoms of TURP syndrome perioperatively. The serum levels of sodium and potassium of all patients were measured 1 h after surgery.
Results
The mean level of serum sodium showed statistically significant reduction (hyponatremia) intraoperatively and postoperatively in group B.
There was a statistically insignificant increase in the mean level of serum potassium (hyperkalemia) intraoperatively and postoperatively in both groups. Electrolyte changes were asymptomatic clinically.
Conclusion
A single dose of conivaptan was found to be effective in preventing a marked decrease in the serum sodium levels in patients undergoing TURP with no effect on the serum potassium level.

Keywords: conivaptan, transurethral resection of prostate surgeries, TURP syndrome


How to cite this article:
Ibrahim AN, Shabana T. Conivaptan prophylactically in transurethral resection of prostate surgeries. Res Opin Anesth Intensive Care 2016;3:157-62

How to cite this URL:
Ibrahim AN, Shabana T. Conivaptan prophylactically in transurethral resection of prostate surgeries. Res Opin Anesth Intensive Care [serial online] 2016 [cited 2020 Jun 4];3:157-62. Available from: http://www.roaic.eg.net/text.asp?2016/3/4/157/195879


  Introduction Top


Symptomatic bladder outlet obstruction and lower urinary tract symptoms caused by benign prostatic hyperplasia are among the most significant problems affecting men [1].

Transurethral resection of prostate (TURP) is the second most common surgical procedure (after cataract extraction) performed in men over the age of 65 years. Endoscopic procedures in the urinary system require the use of irrigating fluids to gently dilate the mucosal spaces, remove blood, cut tissue and debris from the operating field, and enable better vision. Despite the best of efforts to understand and prevent the various complications of endoscopic procedures, incidence of some of the inherent complications has remained the same [2].

The various clinical manifestations, produced because of the absorption of large volumes of irrigating fluid during TURP, are together known as TURP syndrome [3]. The uptake of 1 l of fluid within 1 h corresponds to an acute decrease in the serum sodium concentration of 5–8 mmol/l. Early signs of TURP syndrome are dizziness, headache, nausea, dyspnea, arrhythmias, hypertension, and bradycardia, followed by restlessness and confusion. If not treated promptly, the patient becomes cyanotic, hypotensive, and ultimately sustains cardiac arrest [4].

Despite improvements in the current surgical and anesthetic management, 2.5–20% of patients undergoing TURP show one or more manifestations of TURP syndrome and 0.5–5% die perioperatively. The changes in serum electrolytes also have been correlated with duration of the procedure, volume of 1.5% glycine used, and volume of prostate gland resected [5].

Vaptans, a new group of vasopressin receptor antagonists, are increasingly being used for the treatment of euvolemic, hypervolemic forms of hyponatremia. Conivaptan is now gradually becoming the most popular drug among the vaptans for correction of this condition in the ICU [6].

In our study, we have evaluated the efficacy of a single dose of conivaptan to prevent hyponatremia in TURP patients.


  Patients and methods Top


After obtaining clearance from ethical committee of the institution, this prospective study was conducted on 50 adult consented male patients in Ain Shams University Hospital with American Society of Anesthesiologists (ASA) grades I–III in the age group of 50–80 years, scheduled for elective TURP under central neuraxial block, from July 2015 to March 2016. Patients were randomly allocated to one of the two groups (A and B) (n=25 for each group) using computer-generated sequence of random numbers. Group A patients received intravenous conivaptan 20 mg over 30 min, whereas group B, the control group, received the usual maintenance fluid. All patients were subjected to preanesthetic assessment before TURP surgery. They were assessed with routine investigations for geriatric anesthesia, including hematocrit, ECG, Doppler echocardiography, preoperative serum sodium, and potassium levels (in mEq/l). If needed, the patients were optimized. Patients with pre-existing cardiac or pulmonary diseases and renal dysfunction were excluded from the study. Metastasis in the lumbar spine, a contraindication to central neuraxial block, was also the exclusion criteria. Only patients with prostate volume more than 45 g were included in this study because of the higher incidence of fluid overload and hyponatremia among them. No diuretics were administered in both groups perioperatively.

All patients were preloaded with 10 ml/kg Ringer’s lactate solution, and standard monitors for heart rate, systemic blood pressure, ECG, and SpO2 were attached. Central neuraxial block was performed aseptically at L2–L3 or L3–L4 intervertebral disk space in sitting posture and without difficulty, producing satisfactory analgesia to a dermatome level up to T10. Patients were positioned in lithotomy position and the TURP surgery was started with warm 1.5% glycine irrigation fluid, keeping the irrigation fluid column at a height of 60 cm, measured from the level of pubic symphysis of the patients on the operating table. The duration of the procedure in minutes, the volume of prostate gland resected, and the volume of 1.5% glycine used during the procedure were recorded. Intraoperatively, the serum sodium and potassium levels were recorded in patients after 60 min by blood gas analyzer (Osmetech OPTI CCA-TS; Osmetech: Roswell, GA, USA) using venous blood samples. All patients were carefully observed for the early symptoms of TURP syndrome perioperatively. The procedure was ready to be terminated if serum sodium level was less than 120 mEq/l, serum potassium level was more than 6.0 mEq/l, or with the occurrence of early signs of restlessness, bradycardia, etc.

The serum levels of sodium and potassium of all patients were measured 1 h after surgery.

Statistical analysis

Statistical presentation and analysis of the present study was conducted using the mean, SD, unpaired Student’s t-test, paired t-test, analysis of variance, and χ2-test using SPSS (v.20; SPSS Inc., Chicago, Illinois, USA).

Level of significance: P-values more than 0.05 was considered nonsignificant and less than 0.05 was considered significant.

A group size of 50 was chosen, based on previous studies [5],[6] with an α value of 0.05 and a power of 0.8.

Data were compared using analysis of variance, and continuous data were presented as mean±SD. Data were analyzed using SPSS (version 14.0). Primary outcomes were to detect the changes in serum sodium, whereas the secondary outcome was to detect any changes in serum potassium intraoperatively and postoperatively in the groups.


  Results Top


Mean age, weight, and ASA physical status among patients in groups A and B were comparable and there was no significant difference between them. There was no significant difference between the two groups as regards the volume of the irrigating fluid, the prostate gland resected, and the duration of the TURP surgery ([Table 1]).
Table 1: Demographic and surgical details data

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Preoperative, intraoperative, and postoperative sodium and potassium levels of both groups were also comparable ([Table 2] and [Table 3] and [Figure 1] and [Figure 2]).
Table 2: Na changes perioperatively

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Table 3: K changes perioperatively

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Figure 1: Na changes perioperatively.

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Figure 2: K changes perioperatively

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There was no significant difference between the two groups as regards the preoperative sodium and potassium levels and intraoperative and postoperative potassium levels.

However, there was a significant difference as regards intraoperative and postoperative sodium levels between the two groups. The mean level of serum sodium showed statistically significant reduction (hyponatremia) intraoperatively and postoperatively in group B.

There was a statistically insignificant increase in the mean level of serum potassium (hyperkalemia) intraoperatively and postoperatively in both groups. Electrolyte changes were asymptomatic clinically.


  Discussion Top


On the basis of the results of our study, we suggest that a single dose of conivaptan can be considered for the prevention and even the initial correction of hyponatremia in TURP patients.

Identification of early symptoms of TURP syndrome and prevention are essential to retard the onset of severe and fatal manifestations in patients undergoing endoscopic surgeries [7]. TURP is considered by many as a simpler and safer procedure than open prostatectomy. However, TURP syndrome is one of the serious complications that may occur during this surgical procedure. Patients who have undergone TURP are often elderly and suffer from cardiac, pulmonary, renal, and endocrine disorders. Occasionally, these patients are dehydrated and depleted of essential electrolytes − for example, sodium and potassium − because of long-term diuretics along with restricted fluid intake. Endourological surgery is associated with intraoperative complications of bleeding and deleterious systemic effects because of intravesical absorption of irrigating fluid. Water intoxication with hyponatremia has been postulated by Hahn [3] as the primary cause for the genesis of TURP syndrome.

TURP syndrome is characterized by intravascular volume shifts and plasma–solute (osmolarity) effects. Sodium is essential for the proper functioning of excitatory cells, particularly those of heart and brain. Even with the absorption of small amounts of fluid, hyponatremia may occur in TURP patients because there are several mechanisms that may lead to hyponatremia in these patients:

  1. Dilution of serum sodium through excessive absorption of irrigation solution.
  2. Loss of sodium into the stream of the irrigation fluid from the prostatic resection site.
  3. Loss of sodium into pockets of irrigation solution accumulated in the periprostatic and retroperitoneal spaces.
  4. Larger amounts of glycine stimulate the release of atrial natriuretic peptide in excess of that expected by the volume load, which further promote natriuresis [8],[9],[10],[11].


Symptoms of hyponatremia usually do not develop until the serum sodium concentration decreases below 120 mEq/l. When serum sodium falls below 120 mEq/l, hypotension and reduced myocardial contractility occur. Below 115 mEq/l, bradycardia and widening of QRS complexes, ventricular ectopics, and T wave inversion occur. Below 100 mEq/l, generalized seizures, coma, respiratory arrest, ventricular tachycardia, ventricular fibrillation, and cardiac arrest occur [12].

Madsen and Naber [13] demonstrated another important factor that would also determine the rate of fluid absorption, which will be the hydrostatic pressure at the prostatic bed, depending on the height of the irrigating fluid column and the pressure inside the bladder during surgery. The ideal height of irrigating fluid is 60 cm, so that ∼300 ml of fluid is obtained per minute during resection for good vision. Increase in the prostate size more than 45 g is another factor in developing TURP syndrome [9].

Conivaptan is a nonselective vasopressin receptor antagonist available in an intravenous form and is approved by the Food and Drug Administration to treat euvolemic, hypervolemic hyponatremia [14].

It acts by inhibiting anti- diuretic hormone (ADH) also know as arginine vasopressin (AVP). It competitively and reversibly binds to selected AVP receptors and inhibits actions of ADH. Although conivaptan has high affinity for both V1A (vascular) and V2 (renal) receptors, affinity for V2 is 10-fold higher and the aquaretic effect is predominantly V2-associated [14],[15].

The term aquaretics denotes drugs that can induce electrolyte-free water excretion. V1 receptor antagonism in vascular smooth muscle cells results in vasodilatation, whereas antagonism of V2 receptors present in the renal collecting duct results in aquaresis [16].

Side effects of conivaptan include minimal to clinically significant fall in blood pressure, postural hypotension, and hypokalemia. The most common adverse events reported during studies were dry mouth and thirst [17],[18],[19].

Conivaptan is usually started at a dose of 20 mg intravenous over 30 min, and the maximum daily dose is 40 mg. A single bolus dose of 20 or 40 mg was found to be effective for the correction of acute hyponatremia in neurologically injured patients, and the effect of intermittent bolus dosing lasts up to 72 h [6],[20].

As the incidence of hypervolemic hyponatremia increases in TURP surgeries in patients with prostate volume more than 45 g and with consequent increase in the volume of the irrigating fluid, we studied the effect of single dose of conivaptan to prevent the occurrence of hyponatremia in these patients.

In our study, sodium level decreased in the control group (group B), but luckily it was never below 120 mEq/l, so there were no clinical manifestations. However, in the conivaptan group (group A), there was a marked stability in sodium level that lasted postoperatively. There was a mild statistically nonsignificant increase in potassium levels in the two groups intraoperatively and postoperatively possibly because of intravascular hemolysis from the fluid absorption. Other studies found significant elevation of serum potassium during absorption of 1.5% glycine solution into circulation intraoperatively. The cause of hyperkalemia was inability of 1.5% glycine to maintain the isotonicity of plasma [21],[22].

In our study, such an increase in the potassium levels did not lead to any clinical manifestation.

We did not notice any possible side effects of conivaptan such as hypotension, dry mouth, or thirst.

Although hypertonic saline and loop diuretics are commonly used to treat hypervolemic hyponatremia, their use is associated with serious side effects. Hypertonic saline carries the risk of volume overload in oliguric or anuric patients, and guidelines for rates of infusion have been criticized for posing a risk of underestimating an increase in Na+. Conversely, conivaptan treatment involves a significantly lower volume of medication but carries a higher cost [19].

When diuretics are used routinely or to treat hypervolemia after TURP without careful monitoring of electrolytes, they may worsen hyponatremia and hypo-osmolality. Furosemide and bumetanide act within minutes on the ascending loop of Henle where they inhibit chloride uptake, which causes urinary sodium loss and promotes salt-wasting after TURP [23],[24].

In addition, it should be noted that rapid correction of hyponatremia may lead to central pontine myelinolysis [25].


  Conclusion Top


A single dose of conivaptan was found to be effective in preventing a marked decrease in the serum sodium levels in patients undergoing TURP, especially when there is an increase in the incidence of hyponatremia with an increase in prostate size and the volume of the irrigating fluid.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Te A, Kaplan S. Transurethral electrovaporization of the prostate: the year in review. Curr Opin Urol 1997; 7:25–36.  Back to cited text no. 1
    
2.
Moorthy HK, Philip S. TURP syndrome − current concepts in the pathophysiology and management. Indian J Urol 2001; 17:97–102.  Back to cited text no. 2
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Hahn RG. Fluid and electrolyte dynamics during development of the TURP syndrome. Br J Urol 1990; 66:79–84.  Back to cited text no. 3
    
4.
Hahn RG. Intravesical pressure during fluid absorption in transurethral resection of the prostate. Scand J Urol Nephrol 2000; 34:102–108.  Back to cited text no. 4
    
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Gupta K, Rastogi B, Jain M, Gupta PK, Sharma D. Electrolyte changes: an indirect method to assess irrigation fluid absorption complications during transurethral resection of prostate: a prospective study. Saudi J Anaesth 2010; 4:142–146.  Back to cited text no. 5
    
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Rajan S, Srikumar S, Paul J, Kumar L. Effectiveness of single dose conivaptan for correction of hyponatraemia in post-operative patients following major head and neck surgeries. Indian J Anaesth 2015; 59:416–420.  Back to cited text no. 6
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Mebust WK. Transurethral surgery. In: Walsh PC, Retik AB, Stamey TA, Vaughan ED, editors. Campbell’s urology. Philadelphia: Saunders; 1992. pp. 2900–2919.  Back to cited text no. 7
    
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Mebust WK, Holtgrewe HL, Cockett ATK, Peters PC. Transurethral prostatectomy: immediate and postoperative complications. A cooperative study of 13 participating institutions evaluating 3885 patients. J Urol 1989; 141:243–247.  Back to cited text no. 9
    
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Hahn RG, Stalberg H, Carlström K, Hjelmgvist H, Ullman J, Rundgren M. Plasma atrial natriuretic peptide concentration and renin activity during overhydration with 1.5% glycine solution in conscious sheep. Prostate 1994; 24:55–61.  Back to cited text no. 11
    
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Dominguez M, Perez JA, Patel CB. Efficacy of 3% saline vs. conivaptan in achieving hyponatremia treatment goals. Methodist Debakey Cardiovasc J 2013; 9:49–53.  Back to cited text no. 14
    
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Hline SS, Pham PT, Pham PT, Aung MH, Pham PM, Pham PC. Conivaptan: a step forward in the treatment of hyponatremia? Ther Clin Risk Manag 2008; 4:315–326.  Back to cited text no. 15
    
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Aditya S, Rattan A. Vaptans: a new option in the management of hyponatremia. Int J Appl Basic Med Res. 2012; 2:77–83.  Back to cited text no. 16
    
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Udelson JE, Smith WB, Hendrix GH, Painchaud CA, Ghazzi M, Thomas I et al. Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. Circulation 2001; 104:2417–2423.  Back to cited text no. 17
    
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Ghali JK, Koren MJ, Taylor JR, Brooks-Asplund E, Fan K, Long WA et al. Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab 2006; 91:2145–2152.  Back to cited text no. 18
    
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22.
Moorthy HK, Philip S. Serum electrolytes in TURP syndrome − is the role of potassium under-estimated? Indian J Anaesth 2002; 46:441–444.  Back to cited text no. 22
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Donatucci CF, Deshon GE Jr, Wade CE, Hunt M. Furosemide-induced disturbances of renal function in patients undergoing TURP. Urology 1990; 35:295–300.  Back to cited text no. 23
    
24.
Malone PR, Davies JH, Stanfield NJ, Bush RA, Gosling JV, Shearer RJ. Metabolic consequences of forced diuresis following prostatectomy. Br J Urol 1986; 58:406–411.  Back to cited text no. 24
    
25.
Gravenstein D. Transurethral resection of the prostate (TURP) syndrome: a review of the pathophysiology and management. Anesth Analg 1997; 84:438–446.  Back to cited text no. 25
    


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    Tables

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