The effectiveness of intravenous Lidocaine used to treat pain related to peripheral potassium chloride infusion in adult hospitalized patients: a systematic review protocol Chen Xiao Juan, BSN, AdvDipONO 1 Lim Lay Cheng, BSN, AdvDipONO 1 1. Singapore National University Hospital Centre for Evidence Based Nursing: a Collaborating Centre of the Joanna Briggs Institute Review question/objective Corresponding author: Chen Xiao Juan xiaojuan_chen@nuhs.edu.sg The objective of this review is to identify the effectiveness of intravenous Lidocaine used to treat pain related to peripheral potassium chloride infusion in adult patients in a hospital setting. Background Potassium plays a vital role in the physiological functioning of the human body. Consequently, the level of circulating potassium and other electrolytes in blood is indicative of the wellbeing of the patients. The physiological roles of potassium are as follows: Firstly, it maintains the heart s function by regulating the contraction of skeletal and smooth muscles. Secondly, it causes a direct effect on the cardiovascular system by lowering blood pressure and is suggested to reduce cardiovascular disease mortality. 1-2 Thirdly, potassium may prevent and slow down the progression of renal disease by lowering the urinary excretion of calcium. 4 Finally, it has been suggested that potassium is associated with metabolic syndrome and may play an important role in glucose intolerance. 1-3 Hypokalemia is perhaps one of the most common electrolyte abnormalities in clinical settings. The normal range of serum potassium is 3.5meq/L to 5meq/L. Hypokalemia is defined when the serum potassium level is less than 3.5meq/L and severe hypokalemia is defined when the serum potassium level is less than 2.5meq/L. 4 Hypokalemia reflects a disruption in normal homeostasis and occurs among 20% of hospitalized patients. 5 The most common cause of hypokalemia is the depletion of potassium ions (K+) due to gastrointestinal or urinary losses caused by vomiting, diarrhea, or diuretic therapy; patients receiving diuretics are at a higher risk of developing hypokalemia. 4 The symptoms of hypokalemia generally are not obvious until the serum potassium is below 3.0meq/L. 4 The consequences of hypokalemia include generalized weakness, lack of energy and muscle cramps. Hypokalemia can be life threatening in patients with ischemic heart disease (IHD), heart failure (HF) and left ventricular hypertrophy (LVH), as low potassium is associated with lethal arrhythmias. 6 Therefore prompt intervention is crucial to correct hypokalemia and the goal is to doi: 10.11124/jbisrir-2014-1108 Page 124
prevent and treat life-threatening complications such as arrhythmias, paralysis, rhabdomyosis (muscle weakness) and diaphragmatic weakness. Intervention to treat hypokalemia usually involves oral replacement and intravenous therapy. Oral replacement is usually preferred in the clinical setting because oral replacement is absorbed by the gastrointestinal tract before it turns into serum potassium. Since oral replacement of potassium does not introduce potassium ions into the blood stream, the induced risk of hyperkalemia is extremely low. Hyperkalemia refers to an abnormally elevated level of potassium in the blood. The normal potassium level in the blood is 3.5 to5.0meq/l. 4,7 Potassium levels between 5.1mEq/L and 6.0mEq/L reflect mild hyperkalemia. Potassium levels of 6.1mEq/L to 7.0mEq/L are indicative of moderate hyperkalemia and levels above 7mEq/L indicate severe hyperkalemia. 7 However, in the clinical setting, oral replacement is often restricted by a patient s inability to take medications orally and their gastrointestinal absorption capacity. 4 Therefore, intravenous potassium chloride infusion is often used, and has been proven to be a relatively safe method to correct the condition of hypokalemia in about 20% of the hospitalized patients. 5,6,7 Intravenous infusion of potassium chloride can cause severe acute pain at the infusion site when the administration of infusion is via a peripherally inserted catheter. 9,10,11,12 A peripheral inserted catheter is usually inserted in the veins of the forearm or hand and is less than three inches in length. 8 A central inserted catheter usually ends on the right atrium of the heart or Vena Cava. 8 The infusion of potassium chloride solution via a central catheter will be directed to the heart first before it transports to the rest of the body systems. In other words, the potassium chloride infusion given via a central line does not need to travel through the veins to reach the heart, and as a result of that, it will not cause any pain along the venous pathway. Therefore, this review will only focus on potassium chloride infused via a peripheral catheter; in other words, we can term it as peripheral potassium chloride infusion as the infusion is administered via a peripheral catheter instead of a central catheter (or called it central line). The exact etiology of pain associated with peripheral infusion of potassium chloride is not known. 12 One of the possible etiologies is that potassium chloride is known to be a non-neoplastic irritant agent, 13 and being an irritant agent it will tend to cause irritation to the epithelium of the veins as a result of the irritation it causes pain over the infusion site. Another possible etiology is that peripheral potassium chloride infusion has been associated with higher chances on getting phlebitis, thrombosis, infiltration and extravasation in patients who are receiving such infusion, which can again results in pain at the intravenous site and along the vein. 14 Pain experienced during peripheral potassium chloride infusion is one of the reasons for patients refusing this treatment method. 9,10,11,12 Their refusal of treatment could greatly impact on the continuity of supportive treatment and on treatment outcome. In addition, the discomfort experienced by patients during peripheral potassium chloride infusion may give rise to patients dissatisfaction and/or compliance. According to the Joint Commission International s (JCI) patient care standard, appropriate pain assessment and pain management is a necessity for patients in the acute care setting. 15 As an attempt to increase patients tolerance to peripheral potassium chloride infusion researchers have explored several measures; one of them is the use of Lidocaine either by bolus injection or administering together with the concurrent potassium chloride infusion bag. In particular, in Rapp s study the researchers have added 50mg Lidocaine to KCL 20mmols in 65mls of 0.9% doi: 10.11124/jbisrir-2014-1108 Page 125
saline, whereas in Morrill s study the researchers have added 10mg of Lidocaine into 10momols of KCL in 50mls of 5% dextrose. In both studies patients tolerance to pain have improved significantly. 10,11 In the third study by Lim, instead of administering intravenous Lidocaine as an infusion the researchers have used a bolus dose of 3mls of 1% Lidocaine prior to intravenous peripheral potassium infusion and it is also reported that patients have less pain and better tolerance to potassium chloride infusion. 9 Successful pain management for patients receiving peripheral potassium chloride infusion is an indicator for quality of patient care. Therefore as health care workers, it is our responsibility to ensure the patient s experience is as comfortable as possible when treated in the hospital. It is also our responsibility to find ways and methods to alleviate pain for patients receiving potassium chloride infusion in the hospital setting. A review of the current literature has suggested intravenous administration of lidocaine in managing the pain at the infusion site while infusing intravenous potassium chloride. 9,10,11 Thus far there has not been any systematic review on this topic yet after searching on MEDLINE, EMBASE, Web of Science, CINAHL and the Cochrane Central Register of Controlled Trials. Therefore, the scope of the review will focus on identifying if intravenous Lidocaine is effective in alleviating pain at the infusion site while infusing intravenous potassium chloride via a peripheral inserted catheter. Keywords potassium chloride; pain Inclusion criteria Types of participants This review will consider studies that include all adult patients treated in the hospital setting who are the recipients of peripheral potassium chloride infusion. Adult patients are defined as all participants aged older than 18 years of age. Types of intervention(s) This review will consider studies that evaluate: Intravenous Lidocaine in any dosage including: 1. 1% Lidocaine in 3mls diluent 2. 50mg as a single dose 3. 10mg Lidocaine as a single dose 4. or any other forms Diluents of Lidocaine in any form including: 1. 0.9% saline 2. 0.45% saline 3. 5% dextrose in water doi: 10.11124/jbisrir-2014-1108 Page 126
4. 5% dextrose in 0.9% saline 5. 5% dextrose in 0.45% saline 6. or any other types of diluents Frequency of Lidocaine administration including: 1. in a single dose with any point of infusion 2. as a continuous infusion 3. as in a single dose prior to infusion 4. as a single dose given in the midst of infusion 5. as a single dose given at the end of infusion 6. or any other types of frequencies As described by the primary researchers is effective in alleviating pain for peripheral intravenous potassium chloride infusion. Types of outcomes This review will consider studies that include measurement of pain score by using any validated pain scale described by the primary researchers. Examples of validated pain scales including: 1. pain perception measured by verbal rating scale (VRS) on a scale of 0 to 10 2. visual analogue scale (VAS) that requires a patient to physically mark or indicate on a printed scale 3. Wong-Baker Faces Scale which is designed for use with older patients 4. Behavioural pain assessment scale which is suitable for use with uncommunicative patients. 16 This review will consider any experimental study design including randomized controlled trials, nonrandomized controlled trials, quasi-experimental studies and before and after studies for inclusion. Search strategy The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Studies published in English will be considered for inclusion in this review. Published studies from 1980-2013 will be considered in the review. There is no prior systematic review on this topic, thus we would like to consider any potential study that could have been conducted and this is why the above date range has been selected. The databases to be searched include: MEDLINE CINAHL doi: 10.11124/jbisrir-2014-1108 Page 127
EMBASE Web of Science Cochrane Central Register of Controlled Trials The search for unpublished studies will include: ProQuest Dissertations and Theses US National Institutes of Health, clinical trials Mednar Initial keywords to be used will be potassium chloride and pain Assessment of methodological quality Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer. Data collection Data will be extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives. Data synthesis Quantitative data, where possible, will be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratios (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square. Where statistical pooling is not possible, the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate. Conflicts of interest The reviewers declare no conflict of interest. Acknowledgements The authors would like to acknowledge Dr Dora Lang for her guidance and advice. doi: 10.11124/jbisrir-2014-1108 Page 128
References 1. He, FJ and MacGregor, GA. Potassium: more beneficial effects. Climacteric, 2003; Suppl 3, 36-38 2. He, FJ and MacGregor, GA. Beneficial effects of potassium on human health. Physiol Plant. 2008; 133(4): 725-735. 3. Moon, HK and Kong, JE. Assessment of nutrient intake for middle aged with and without metabolic syndrome using 2005 and 2007 Korean National Health and Nutrition Survey. The Korean Journal of Nutrition.2010; 43(1): 69-78. 4. Mount BD. Clinical manifestation and treatment of hypokalemia. Wolters Kluwer Health.2013 5. Gennari, FJ. Disorders of potassium homeostasis: hypokalemia and hyperkalemia. Crit Care Clin. 2002; 18(2): 273-288. 6. Unwin, RJ, Luft, FC, Shirley, DG. Pathophysiology and management of hypokalemia: a clinical perspective. Nat Rev Nephro. 2011; 7(2): 75-84. 7. Melissa, CS. Medicinenet: hyperkalaemia. [Electronic report] 2013.[Cited 2014 Aug 4 ]; 8. Health care infection control practices advisory committee. Guidelines for the Prevention of Intravascular Catheter-Related Infections: Terminology and Estimates of Risk. [Electronic report] 2011. [Cited 2014 Aug 4 ]; 9. Lim, ET, Khoo, ST, Tweed, WA, Kloo, ST. Efficacy of lignocaine in alleviating potassium chloride infusion pain. Anaesth Intensive Care.1992; 20(2): 196-8. 10. Morill, GB. and Katz, MD. The use of lidocaine to reduce the pain induced by potassium chloride infusion. J Intraven Nurs.1988; 11(2): 105-108. 11. Rapp, RP. Use of lidocaine to reduce pain associated with potassium chloride infusions. Clin Pharm.1987; 6(2): 98. 12. Chan, R. and Armstrong, D. Peripheral intravenous infusion of potassium chloride: effect of solution composition on infusion-site pain. Canadian J Hosp Pharm. 2004; 57(1): 27-31. 13. Avdal, E. Ü. and N. Aydinoğlu. Extravasations of Vesicant/Non-Vesicant Drugs and Evidence Based Management.Inte J.2012. 5(2):1b. 14. Michelle Franklin, B., et al. Infiltration and Extravasation: Update on Prevention and Management.J Infus Nurs.2009; 32(4):203-211. 15. The Joint Commission International. International Patient Safety Goal: Patient pain management. [Electronic Report] 2015. [cited 2014 Aug 4]; 16. Jaywant, Shailaja S., and Anuradha V. Pai. A comparative study of pain measurement scales in acute burn patients. Indian J Occup Ther.2003. 35(3): 13-7. doi: 10.11124/jbisrir-2014-1108 Page 129
Appendix I: Appraisal instruments MAStARI appraisal instrument this is a test message doi: 10.11124/jbisrir-2014-1108 Page 130
Appendix II: Data extraction instruments MAStARI data extraction instrument doi: 10.11124/jbisrir-2014-1108 Page 131