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A Comparison of the Effects of Lidocaine or Procaine containing St. Thomas No. 2 Cardioplegia Solution on Post-operative Renal Function

Article Information

Vipin Balachandran*, Xinrui Zhou, Linna Huang, Rebecca Tee, Priyanka Paul, John Dittmer, Marcus Bayly, Sarah Armarego, Taranpreet Singh, Peng Seah, Allen James

Department of Cardiothoracic Surgery, John Hunter Hospital, Lookout Road, New Lambton Heights, Newcastle 2287, Australia

*Corresponding author: Vipin Balachandran, Department of Cardiothoracic Surgery, John Hunter Hospital, Lookout Road, New Lambton Heights, Newcastle 2287, Australia

Received: 15 March 2020; Accepted: 23 March 2020; Published: 30 March 2020

Citation: Vipin Balachandran, Xinrui Zhou, Linna Huang, Rebecca Tee, Priyanka Paul, John Dittmer, Marcus Bayly, Sarah Armarego, Taranpreet Singh, Peng Seah, Allen James. A Comparison of the Effects of Lidocaine or Procaine containing St. Thomas No. 2 Cardioplegia Solution on Post-operative Renal Function. Cardiology and Cardiovascular Medicine 4 (2020): 105-110.

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Abstract

Acute kidney injury (AKI) is one of the most common complications after cardiac surgery and is thought to result as a complex interplay between peri-operative factors. The effects of cardioplegia on renal function have not been well defined. We compared the effects of St. Thomas No. 2 cardioplegia solution modified with lidocaine or procaine and found no statistically significant difference in between the two groups. We carried out further multivariate testing adjusting for diabetes and found no statistically significant changes in renal function between the two groups.

Keywords

Cardioplegia; Renal failure; Lidocaine; Procaine; St. Thomas No. 2

Cardioplegia articles, Renal failure articles, Lidocaine articles, Procaine v, St. Thomas No. 2 articles

Article Details

Introduction

Acute kidney injury (AKI) is one of the most common complications after cardiac surgery and has been reported at various rates between 1-30% and is associated with increased morbidity and mortality [1-3]. The mechanism behind AKI after cardiac surgery is not well defined and is thought to be the result of a complex interaction between peri-operative factors [1,2,4].

Whilst many studies that look at pre-operative risk factors for the development of renal failure exist, intraoperative factors have not been well investigated [5-7]. Currently in global literature, the association between different cardioplegia solutions and AKI has not been examined.

In this study, we look at the effects of St-Thomas Solution No. 2 cardioplegia modified with lidocaine or procaine on post-operative renal function. We also hypothesise that diabetes will have an additive effect in addition to cardioplegia in negatively affecting renal function.

Study Design

Institutional approval was gained for the modification of our standard cardioplegia solution with either lidocaine or procaine. Both solutions were compounded by Baxter International (Deerfield, IL, USA).

The standard cardioplegia solution composition is given below in Table-1 to which either 1mmol lidocaine (AHK 5560) or procaine Hydrochloride (CP 5537) was added.

All patients undergoing cardiac surgery at our institution between March 2016 – 2017 were included in this study. Cases that were done without the use of CP 5537 or AHK 5560 were excluded. Our database contained 126 patients with 79 people being administered CP 5537 and 47 individuals receiving AHK 5560. Randomisation was not possible due to surgeon preference.

The anaesthetic and perfusion protocols were the same between both groups. Non pulsatile cardiopulmonary bypass was used to provide a mean arterial pressure of 50mm Hg. All operations were done using a LivaNova S5 pump using cold blood cardioplegia at a ratio of four parts blood and one part cardioplegia solution. Antegrade and retrograde delivery routes were used where possible and re-dosing was done at 20 minute intervals with half strength (8:1) solutions. Patients were passively cooled to 28°C and actively warmed to 37°C on separation from bypass.

Renal function (viz. creatinine, urea and eGFR) was measured on post-operative days 0, 1 and 5 in keeping with unit protocols. CKD was diagnosed as defined in the 2012 KIDGO guidelines.

Results were analysed in SPSS v.26 and are presented as mean ± standard deviation unless specified otherwise. For brevity, comparisons have been reported as CP 5537 results vs. AHK 5560 results.

Two statistical tests were used in this study: one way repeated measures ANOVA using Mauchly’s test of sphericity and a 2-way ANOVA using Levene’s test of Equality. A p value of 0.05 was considered statistically significant.

Results

Sodium 77mmol

Potassium 40mmol

Magnesium 15mmol

Chloride 149mmol

Glucose 11mmol

Sodium bicarbonate 25mL 8%

Table 1: Standard Cardioplegia Solution (added to 1L normal saline by volume)

 

Cardioplegia Type

CP 5537

AHK 5560

Mean

Count

Mean

Count

Age of patient

65

 

67

 

Sex

Male

 

58 (73.4%)

 

39 (83%)

Female

 

21 (26.6%)

 

8 (17%)

Diabetic Status

Diabetic

 

24 (30.4%)

 

13 (27.7%)

Not Diabetic

 

55 (69.6%)

 

34 (72.3%)

Chronic Kidney Disease

Stage 2

 

38 (48.1%)

 

25 (53.2%)

 

Stage 3a

 

9 (11.4%)

 

7 (14.9%)

 

Stage 3b

 

6 (7.6%)

 

4 (8.5%)

 

Stage 4

 

2 (2.5%)

 

0

 

Stage 5

 

2 (2.5%)

 

1 (2.1%)

Preoperative Dialysis

 

2

 

1

AXC Time

63

 

59

 

CPB Time

98

 

92

 

Pre Op Creatinine

112

 

110

 

Pre Op Urea

7.3

 

7.0

 

Pre Op eGFR

70

 

71

 

CPB: Cardiopulmonary Bypass Time (min); AXC: Aortic Cross Clamp Time (min); Creatinine (μmol/L); Urea (mmol/L); estimated GFR as calculated by the Cockcroft-Gault Equation (mL/min/1.73m2)

Table 2: Clinical Characteristics.

   

df

Mean Square

F

P

Partial η2

Creatinine

Time*CP

1.540

1464.479

.889

.389

.007

Error

187.887

1646.473

     

Urea

Time*CP

1.596

2.434

.241

.735

.002

Error

193.084

10.084

     

eGFR

Time*CP

2.493

64.901

.761

.494

.006

Error

301.602

85.265

     

Time: Repeated measures on post operative days 0, 1 and 5; CP: cardioplegia; df: degrees of freedom

Table 3: Repeated measures ANOVA after Greenhouse-Geisser Correction

Discussion

Our patient base had a similar demographic profile compared to other major centres in Australia, having a mean age of 65.6±10.6 years and a male majority (n=97; 76.9%). 37 (29.4%) patients were diabetic with comparable spreads across both cardioplegia groups.

94 (74.6%) patients had some degree of CKD and three patients had stage 5 CKD requiring dialysis. Stage 1 CKD was not reliably identified in our study group. Pre-operative creatinine, urea and eGFR were similar between both groups (112±121 vs. 110±122 μmol/L; 7.3±3.4 vs. 7±3.9 mmol/L; 70±21 vs. 71±20 mL/min/1.73m2).

Although not mentioned explicitly in the results section, there were a mix of cases including coronary artery bypass grafts, valve replacements and aortic operations including emergency management of Type – A dissections. All urgency classifications as per the ANZSCTS database were included in the study [8]. Total cardiopulmonary bypass and aortic cross clamp times were similar between both groups (98±38 vs. 92±32 mins; 63±33 vs. 59±28 minutes).

A one-way repeated measures ANOVA was performed to determine if there was a statistically significant difference in the post-operative day 0, 1, 2 and 5 creatinine, urea and eGFR tests between the two cardioplegia groups. The assumption of sphericity was not met in all three tests (Mauchly’s test of sphericity: χ2(5) = 194.2, p <0.001; χ2(5) = 200.8, p <0.001; χ2(5) = 40.9, p <0.001). Epsilon was calculated according to Greenhouse and Geisser in all three cases and used to correct the ANOVA. Statistically significant changes were not noted in creatinine [F(1.540, 187.887) = 0.889, p=0.389], urea [F(1.596, 193.084) = 0.241, p=0.735] and eGFR [F(2.493, 301.602) = 0.761, p=0.494] between the two cardioplegia types. Further post-hoc tests were therefore not carried out.

A 2 way ANOVA was then performed to examine the effects of diabetes on the change of creatinine, urea and eGFR between pre-operative and post-operative day 5 levels. Statistically significant interactions between diabetic status and cardioplegia type were not noted in creatinine [F(1, 122) = 2.709, p = 0.102, partial η2 =0.22], urea [F(1, 122) = 2.312, p = 0.131, partial η2 =0.19] and eGFR [F(1, 122) = 2.709, p = 0.102, partial η2 =0.22]

In conclusion, we have found no significant differences in the post-operative renal function when using procaine or lignocaine enriched cardioplegia solutions. Patients with pre-existing CKD remained within their classification and any transient AKI resolved by the 5th postoperative day without targeted therapy. Neither group had cases who had to be commenced on temporary or new long-term dialysis.

There are several limitations to this study and the field in general that need to be addressed. First, the lack of randomisation due to institutional factors is sub-optimal even though this was a prospective study. Pre-existing CKD caused a significant number of outliers making statistical modelling difficult. Cardiopulmonary bypass may contribute to AKI in various ways including activation of pro-inflammatory cytokines, hypoperfusion etc. Temperature has also not shown to be a significant factor in the development of renal failure but may affect hypoperfusion in general. Finally, as with all but the largest of studies, larger patient cohorts can improve the power of the study [5].

Conclusion

No statistically significant reduction in renal function was seen when comparing St. Thomas No. 2 cardioplegia solution modified with lidocaine vs. procaine. We also did not find a statistically significant reduction in renal function when adjusting for the presence or absence of diabetes.

Ours is the first study that we are aware of that has investigated relatively common modifications to the St. Thomas No. 2 cardioplegia solution within the context of renal dysfunction after cardiac surgery. The authors hope that further studies can be undertaken to build on these results.

References

  1. Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, Bauer P, et al. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: A prospective cohort study. Journal of the American Society of Nephrology 15 (2004): 1597-1605.
  2. Loef BG, Epema AH, Smilde TD, Henning RH, Ebels T, Navis G, et al. Immediate postoperative renal function deterioration in cardiac surgical patients predicts in-hospital mortality and long-term survival. Journal of the American Society of Nephrology 16 (2005): 195-200.
  3. Schopka S, Diez C, Camboni D, Floerchinger B, Schmid C, Hilker M. Impact of cardiopulmonary bypass on acute kidney injury following coronary artery bypass grafting: a matched pair analysis. J Cardiothorac Surg 9 (2014): 20.
  4. Conlon PJ, Stafford-Smith M, White WD, Newman MF, King S, Winn MP, et al. Acute renal failure following cardiac surgery. Nephrology Dialysis Transplantation 14 (1999): 1158-1162.
  5. Provenchère S, Plantefeve G, Hufnagel G, Vicaut E, de Vaumas C, Lecharny J-B, et al. Renal dysfunction after cardiac surgery with normothermic cardiopulmonary bypass: incidence, risk factors, and effect on clinical outcome. Anesthesia & Analgesia 96 (2003): 1258-1264.
  6. Dobson GP, Faggian G, Onorati F, Vinten-Johansen J. Hyperkalemic cardioplegia for adult and pediatric surgery: end of an era? Frontiers in Physiology 4 (2013): 228.
  7. Shaw AMBFF. Update on acute kidney injury after cardiac surgery. Journal of Thoracic and Cardiovascular Surgery 143 (2012): 676-681.
  8. In: ANZSCTS National Cardiac Surgery Database Program. Data Definitions Manual. 2017

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