lactate peritoneal dialysis solutions for the treatment of infusion pain
Bicarbonate and bicarbonate/lactate peritoneal dialysis solutions for the treatment of infusion pain
Robert A Mactier, Timothy S Sprosen, Ram Gokal, Paul F Williams, Marianne Lindbergh, Ramesh B Naik, Ulf Wrege, Knut Christian Gr Rutger Larsson, Jonas Berglund, Anders P Tran and Dirk FaictCorrespondence: Dr Robert A. Mactier, Stobhill Hospital NHS Trust, Balornock Road, Glasgow, Scotland, United Kingdom
Received 30 May 1997; Revised 7 November 1997; Accepted 10 November 1997.
Top of pageAbstractBicarbonate and bicarbonate/lactate peritoneal dialysis solutions for the treatment of infusion pain. A randomized, double blind, cross over study was undertaken to determine the effects of novel bicarbonate (38 mM) and bicarbonate (25 mM)/lactate (15 mM) containing peritoneal dialysis (PD) solutions on infusion pain in patients who experienced inflow pain with conventional lactate (40 mM) solution. Pain was assessed using a verbal rating scale and the validated McGill Pain Questionnaire (MPQ). Eighteen patients were recruited to the study. Both novel solutions resulted in highly statistically significant reductions in inflow pain compared to the control lactate solution, as assessed with both the verbal rating scale and the MPQ. For all pain variables assessed, the bicarbonate/lactate solution was more effective than the bicarbonate solution in alleviating pain. In conclusion, both solutions reduced the infusion pain experienced with control solution, but the bicarbonate/lactate solution appears to be the most effective. In contrast to the most widespread current treatment, which is the manual injection of sodium bicarbonate, the bicarbonate/lactate solution does not have the associated increased risk of peritonitis.
Keywords: pain and dialysis, dialysate and pain, bicarbonate dialysate, lactate, bicarbonate dialysate, McGill Pain Questionnaire, infusion pain, peritonitis, abdominal pain
Abdominal pain is a common complication of peritoneal dialysis (PD), with a multifactorial etiology1,23. For example, it has been reported that abdominal pain occurs in 78% of patients during an episode of peritonitis4. However, pain experienced during intraperitoneal infusion of the dialysis solution also occurs in the non peritonitis state, and is distinguished by the abdominal pain appearing within the first minute or so after starting infusion of the PD solution, but which generally diminishes during the dwell5. Infusion pain is usually observed in new patients commencing dialysis and is often transient in nature, spontaneously disappearing over time3,6. However, it is established that infusion pain can remain a troublesome complication in PD patients and in the most extreme cases can result in the discontinuation of PD7.
Infusion pain is generally believed to be due to the acidity (pH 5.2 to 5.5) of conventional lactate buffered dialysis solutions. Such solutions not only contain high concentrations of lactate, but also glucose and are acidic to minimize caramelization as well as the chemical transformation of glucose to 5 hydroxymethylfurfural and its acidic metabolites7,8. Other factors that may contribute to infusion pain include the position of the catheter, the temperature of the dialysis solution2, and the presence of high glucose concentrations in the PD fluid, as it is not uncommon for patients to predominantly experience pain during the infusion of hypertonic solutions7.
A number of actions can be employed to alleviate infusion pain. By far the most common treatment is the neutralization of the PD solution by the manual injection of sodium bicarbonate into the solution immediately prior to infusion. Sodium bicarbonate is preferred to other bases, such as hydroxide, or sodium carbonate because of its safety, buffering action and gradual titration curve9. A number of reports have adidas originals demonstrated the effectiveness of such manual injection in alleviating infusion pain8,10,11. However, the need to inject into every bag prior to infusion adds to the therapy burden for the patient and also increases the overall treatment cost. The greatest concern, however, is related to the possibility that peritonitis rates are greatly increased in patients who manually inject sodium bicarbonate due to external contamination of the solution. For example, in a study by Henderson, Couper and Lumsden7, the peritonitis rate in 10 patients injecting bicarbonate for the treatment of inflow pain was 1 episode/4 patient months. Following cessation of bicarbonate treatment, the peritonitis rate decreased to 1 episode/9 patient months. Other possible actions that may be employed to treat inflow pain include slowing the infusion rate, incomplete drainage (including the use of tidal therapy in automated peritoneal dialysis), manual injection of local anesthetics into the solution prior to infusion, catheter replacement, and in the most extreme cases transfer to hemodialysis2.
The ideal PD solution would have a neutral pH to prevent the occurrence of infusion pain and the need to manually inject sodium bicarbonate. In the present study, two new solutions with a physiological pH were evaluated. Both solutions have a pH 7.0 to 7.4, and in one solution the lactate buffer of conventional solutions has been replaced with a 38 mM bicarbonate buffer, and in the other solution a combined 25 mM bicarbonate/15 mM lactate buffer is utilized. The new solutions are presented in a two chambered bag configuration to separate calcium and magnesium from bicarbonate to avoid precipitation. The contents of the two chambers are mixed prior to administration. The aim of the present study was to assess the effectiveness of these two new solutions in alleviating inflow pain in patients who experienced such pain using conventional lactate containing PD solution using a randomized, double blind, cross over design.
Top of pageMETHODSParticipating centersThe study had a prospective, randomized, double blind, cross over design, where test and control solutions were studied during single dwells. A total of 18 patients were recruited from 8 participating centers (N is the number of patients recruited at each center): Stobhill Hospital, Glasgow, United Kingdom (N = 4); Manchester Royal Infirmary, United Kingdom (N = 5); Addenbrooke’s Hospital, Cambridge, United Kingdom (N = 3); Royal Berkshire Hospital, Reading, United Kingdom (N = 1); Lasarettet, H Sweden (N = 2); M Eskilstuna, Sweden (N = 1); L G Sweden (N = 1); Universitetssjukhuset, Link Sweden (N = 1). The study protocol was approved by the Ethics Committee of each participating center.
Study populationPatients were recruited to the study if they were at least 18 years old, gave fully informed consent to partic adidas originals ipate, and experienced repeated infusion pain that based on medical judgement was not related to the catheter or excessive intraperitoneal volume of dialysis fluid. Patients could not participate in the study if they had been treated for peritonitis within the previous 30 days.
Eighteen patients were recruited to the study. One patient withdrew due to transplantation during the study and was excluded from the statistical analysis. The mean age of patients at entry was 53.5 years, with a mean time on PD of 1.7 years and the mean length of time since first experiencing inflow pain was 16.4 months. Eleven of the 18 patients regularly used hypertonic glucose solution of at least 3.86%, and two patients commented that the infusion pain that they experienced was associated with the use of the 3.86% glucose solution (see below). There was a large variation within the eight participating centers in the frequency with which infusion pain was observed within each center’s total CAPD population. The mean frequency across all centers was 1 in 25 (range 1 in 3 to 66) patients.
Half of the patients had experienced at least one episode of peritonitis in the previous six months. Two thirds of the patients regularly injected alkalizing agents into their PD bags prior to infusion. The 12 patients who regularly injected alkalizing agents had a much higher incidence of peritonitis (1 episode/6 patient months), when compared with the 6 patients who did not regularly inject (1 episode/18 patient months). However, due to the small sample size this difference failed to reach statistical significance (P = 0.131, unpaired t test).
Study procedures and test solutionsPatients attended the participating hospital dialysis clinic for all study exchanges. Within a one to three week period, patients were evaluated during two dialysis exchanges with each test solution in random order. Thus, all patients were to undergo six separate study dwells; patients could undertake a maximum of two test evaluations in one day, but it was required that these study exchanges were separated by a routine dwell (40 mM lactate solution) of at least four hours. All dwells were required to be of at least three hours and all evaluations were undertaken using a 3.86% glucose solution, as a previous study has suggested that infusion pain occurs more frequently with the use of hypertonic glucose solutions7. The composition of the three solutions is given in Table 1. The identity of the solution under evaluation was unknown to the patient as well as the study nurse. The randomized schedule for solution administration for each patient was only known by an attending nurse who prepared and blinded the test bag prior to infusion (by the use of an opaque overpouch). No alkalizing agents (that is, manual injection of sodium bicarbonate) were permitted to be added prior to the infusion of any of the three solutions under investigation.
Pain assessmentPain was assessed by two methods. A five point verbal scale (0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain, 4 = very severe pain) was administered to assess pain intensity at the following time points: start of infusion, 1, 3, and five minutes after start of infusion, end of infusion, 10, 30 minutes and end of dwell, and start, five minutes and end of drain. Peak pain during the period of infusion, dwell and drain was defined as the most intense pain recorded with the five point verbal scale during each period.
In addition, the validated McGill Pain Questionnaire (MPQ)12,13 was completed by the patient after 40 minutes of the dwell. The MPQ was selected as the most suitable instrument for the assessment of inflow pain following a systematic search and review procedure, which identified 27 questionnaires that could potentially be suitable for use in the present study. The MPQ was selected because of its demonstrated validity, reliability and sensitivity, and the fact that it had previously successfully been used in a dialysis population14. The MPQ aims to capture not only the unidimensional aspects of pain related to the severity of the experience alone, as it now well established that pain is multidimensional and the severity or intensity of the sensory response is only one component. Thus, pain also has affective and evaluative dimensions which disrupt ongoing behavior a adidas originals adidas originals nd thought. Consequently, Melzack and Casey have postulated that there are three major dimensions of pain, namely the sensory discriminative, motivational affective, and cognitive evaluative dimensions of pain15. All of these dimensions of pain are evaluated using the validated MPQ. Previous types of pain studies undertaken using the MPQ have shown that different types of pain (that is, headache, labor pain) have a unique profile in terms of their effects on the different MPQ dimensions and this has been used to discriminate between different types of pain15.
Safety was followed throughout the study by monitoring for adverse events.
Statistical analysisPatients were included in the statistical analysis only if they completed the study (that is they received all of the six study exchanges). Including patients in the analysis who dropped out from the study could introduce a potential source of bias, as all patients would not receive the same number of study exchanges with each test solution. An initial analysis of variance (ANOVA) was undertaken with terms for patients, periods (the relative position of the six dwells), treatment and carryover16. If the carryover effect was significant at the P = 0.20 level, then an analysis was to be used to estimate and test the differences between the treatments. An analysis of variance (ANOVA) was used as it was considered the most appropriate methodology because it enabled estimates of treatment differences between the three test solutions to be made after allowing for all other factors in the design of the study. These other factors were: (1) differences between patients and participating centers; (2) differences between treatment periods (that is, the order of administration of the test solutions); and (3) any potential carryover effect by which the treatment given at one exchange might influence the results of subsequent evaluations. If no account were taken of these factors, for example, if a paired or unpaired t test had been utilized, the results could be potentially misleading as the analysis would take no account of the factors above, which could potentially bias the results observed.
The actual study design was unbalanced due to one patient dropping out from the study and, therefore, the three solutions were not evaluated with equal frequency at each of the six single dwell positions. The results presented are the actual mean for each treatment adjusted after allowing for any possible differences as a result of the unbalanced administration. The adjusted mean was not significantly different from the actual mean for all variables assessed. Each patient was evaluated with each solution on two separate occasions and, therefore, the number of observations are exactly twice the number of patients analyzed. A P value less than 0.05 was considered statistically significant.
Top of pageRESULTSThe pain severity time profile as assessed using the five point verbal rating scale was typical of inflow pain Figure 1, with the most severe pain being observed during the first few minutes of infusion and then reducing in severity during the course of the dwell, and no pain being experienced during the later part of the dwell and drain.
Full figure and legend (22K)
The majority of patients experienced inflow pain with the control solution as assessed using the verbal rating scale Figure 2. The 17 evaluable patients were evaluated during two dialysis exchanges with each test solution in random order. All 17 evaluable patients met the entry criteria of experiencing repeated pain on infusion, but the pain response recorded with the control solution during the study showed a degree of variability in that no pain was recorded on 6 of 34 (18%) test evaluations upon infusion of the control lactate solution. Further, each patient was evaluated during two dialysis exchanges with the control solution in a random double blind manner, and it is interesting to note that two patients experienced no pain during both exchanges, while a further two patients experienced no pain on only one of the exchanges with the control solution.