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OPEN ACCESS Asian Journal of Animal and Veterinary Advances

ISSN 1683-9919DOI: 10.3923/ajava.2017.288.293

Research ArticleIntradialytic Complications in Dogs with Acute Renal FailureSubmitted to Intermittent Hemodialysis1Alessandra Melchert, 2Pasqual Barretti, 1Priscylla Tatiana Chalfun Guimarães Okamoto, 2André Luis Balbi,2Luis Cuadrado Martin, 3Sheila Canevese Rahal, 4Andre Marcelo Conceição Meneses,1Silvano Salgueiro Geraldes and 1Paula Bilbau Sant'Anna

1Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science, Universidade Estadual Paulista (UNESP), Botucatu,18618-970 São Paulo, Brazil2Department of Medical Clinic, School of Medicine, Universidade Estadual Paulista (UNESP), Botucatu, 18618-970 São Paulo, Brazil3Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science,Universidade Estadual Paulista (UNESP), Botucatu, 18618-970 São Paulo, Brazil4Institute of Animal Health and Production, Universidade Federal Rural da Amazônia (UFRA), 66077-530 Belém, Pará, Brazil

AbstractBackground and Objective: Intermittent hemodialysis (IHD) is a procedure that can sustain a patient’s life during acute renal injury (ARI).However, there are some complications related to this procedure. The aim of this study was to evaluate clinical changes and maincomplications seen in dogs with acute renal failure (ARF) treated by short daily hemodialysis, during the intradialytic period.Materials and Methods: Eight male crossbred dogs, aged 1-5 years, with body mass from 6-20 kg, with ARF (serum creatinineconcentration greater than 5 mg dLG1) were evaluated. The dogs received daily treatment with intermittent hemodialysis for 9 days, with60 min sessions in conscious dogs. Repeated measure ANOVA was performed to evaluate clinical parameters during hemodialysis sessionsand paired t-test was used to compare hematological parameters in pre- and post-dialytic periods. Results: No changes in heart rate andrespiratory rate were observed, while decrease in temperature and systolic arterial pressure were noted during intermittent hemodialysis.In 3 dogs (37.5%), neurological alterations were noted. The intradialytic intercurrences observed were vomiting in 22.22% of theintermittent hemodialysis sessions, hypotension in 15.27% and the need to exchange the dialysis catheter in 5.55% of the sessions. Allthe intercurrences presented were easily corrected. Conclusion: Intermittent hemodialysis is a safe therapy that is associated with a lowincidence of complications in dogs.

Key words: Acute kidney injury, azotemia, renal replacement therapy, hemodialysis, complications

Received: July 27, 2017 Accepted: September 19, 2017 Published: October 15, 2017

Citation: Alessandra Melchert, Pasqual Barretti, Priscylla Tatiana Chalfun Guimarães Okamoto, André Luis Balbi, Luis Cuadrado Martin, Sheila Canevese Rahal,Andre Marcelo Conceição Meneses, Silvano Salgueiro Geraldes and Paula Bilbau Sant'Anna, 2017. Intradialytic complications in dogs with acute renal failuresubmitted to intermittent hemodialysis. Asian J. Anim. Vet. Adv., 12: 288-293.

Corresponding Author: Alessandra Melchert, Department of Veterinary Clinic, School of Veterinary Medicine and Animal Science,Universidade Estadual Paulista (UNESP), Botucatu, 18618-970 Sao Paulao, Brazil Tel: +55 14 38802194

Copyright: © 2017 Alessandra Melchert et al. This is an open access article distributed under the terms of the creative commons attribution License, whichpermits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

Competing Interest: The authors have declared that no competing interest exists.

Data Availability: All relevant data are within the paper and its supporting information files.

Asian J. Anim. Vet. Adv., 12 (6): 288-293, 2017

INTRODUCTION

Intermittent hemodialysis (IHD) is a therapeutic procedureused to manage biochemical and fluid disorders of uremia1.The method uses extra-body circulation to filtrate the bloodthrough a semi permeable artificial membrane2, to relieveazotemia, metabolic disorders and the accumulation of liquidsand toxic solutes1.

The major application of IHD in veterinary medicine is insupportive management of uremia resulting from acute renalfailure (ARF)3,4 or chronic kidney disease1 when conventionaltherapies are not effective4,5 and reduces mortality rate inARF6. Moreover, it is useful for fluid removal to manage overhydration1, in acute intoxication and drug over doses and tomanage kidney failure in leptospirosis7.

However, IHD is not an innocuous procedure and may beassociated with a wide variety of complications8. The maincomplications include, hypotension due large extracorporealblood volume or ultrafiltration during HDI sessions1, problemswith vascular access, such as thrombosis or failure to provideadequate blood flow8, neurologic signs or seizures due dialysisdisequilibrium syndrome5 and gastrointestinal, respiratory andhematologic alterations8. Gastrointestinal signs such as nauseaand vomiting are common and may be a complication ofdialysis-induced hypotension1. Hematologic complicationsinclude anemia, thrombocytopenia and leucopenia8.

Few studies have evaluated hemodialysis complicationsin dogs5,7. However, these studies reveal a heterogeneouscondition of renal dysfunction and the side effects ofhemodialysis are varied5,7. Additionally, intermittenthemodialysis (alternate-day) is widely used asrenal-replacement therapy in animal patients with ARF8, butan adequate dose has not been defined. In humans, dailyintermittent hemodialysis showed improvement in patientsurvival with few complications6. To our knowledge, this isthe first controlled study evaluating the hemodialysiscomplications in a group of dogs with similar renaldisfunction, using a short-duration daily hemodialysis sessions.

Therefore, this study aimed to evaluate the complicationsobserved during the intradialytic 60 min hemodialysissessions, performed as renal replacement therapy in dogs withARF.

MATERIALS AND METHODS

Animals: The study was approved by the Ethics Committee ofBotucatu Medical School, Universidade Estadual Paulista(UNESP). Eight crossbred dogs were used, aged 1-5 years,male, clinically healthy, with body mass from 6-20 kg. They

were induced to ARF using gentamicin (Gentocin, ScheringPlough, Brazil) based on the experimental model previouslyreported9.

Procedures: This study was conducted from January,2011-March, 2013. Once ARF had developed (serum creatinineconcentration greater than 5 mg dLG1), daily treatment wasstarted with IHD for 9 days (from M1-M9), with 60 min sessionsin conscious dogs. The extra corporeal blood flow rate wasrestricted to 3-5 mL kgG1 minG1 in the first two initialtreatments, to avoid dialysis disequilibrium and to about10-15 mL kgG1 minG1 after the third session of IHD. Vascularaccess to blood filtration was obtained by implanting atranscutaneous double-lumen venous dialysis catheter(two-Lumen Central Venous Catheterization Set, ArrowInternational Inc., USA) in the jugular vein, as described beforeby Cowgill and Langston1.

It was used a proportioning system IHD machine, withcontrolled UF (system 1000 Series; Baxter, USA)10 and ahollow-fiber hemodialyzer, with a polysulfone membrane(Hemoflow F3; Fresenius Medical Care, Germany). To make aconnection with the extra corporeal circuit, it was filled withisotonic saline (priming of 180 mL) which was infused at thebeginning of IHD. Dialysate solution was composed of sodiumbicarbonate as the buffer solution. Anticoagulation during IHDwas achieved with sodium heparin (Liquemine; Roche,Switzerland), at 100 U kgG1.

During IHD, the following parameters were analyzed,heart rate (HR) in beats minG1 (bpm), respiratory rate (RR) inbreaths minG1 (bpm) and rectal temperature (T) in ECelsius(EC), monitored at the following times: Beginning of dialysis(T0) and at 5, 30 and 60 min of IHD (T5, T30 and T60). Thesystolic arterial pressure (SAP) (mmHg) was measured at T0, T5and T60. The standard values established for dog were used asreference. All intercurrences during IHD were noticed.

In pre- and post-dialytic periods, the hematocrit (Hct) (%),white blood cell count (WBC) (×103 mmG3) and platelet count(×103 mmG3) were evaluated considering the reference rangefor the species.

Hypotension episodes (SAP <100 mmHg)11 were treatedwith 100 mL isotonic saline solution by intravenous (IV)administration. If hypotension was maintained, mannitol(Manitol, Baxter, USA) at a dosage of 1 g kgG1 IV, wasadministrated. Neurological changes (misdirection,vocalizations) were treated with 1 g kgG1 of mannitol IV andconvulsive episodes, with diazepam (Valium, Roche,Switzerland) 1 mg kgG1 IV, twice, if needed. Hypothermia wastreated by warming the animal. When the vascular access waslost, the catheter was changed with a wire guide at theprevious access site.

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Statistical analysis: Parametrical variables were expressed asmean and standard-deviation (SD). Repeated measuresANOVA with the Tukey post hoc test were performed toevaluate clinical parameters (T0, T5, T30 and T60) during HDsessions (M1-M9). A paired t-test was used to comparehematological parameters in pre- and post-dialytic periods.The Kolmogorov-Smirnov test was used to check the normaldistribution of the haematological data. The p<0.05 wasconsidered significant.

RESULTS

In 72 sessions, intradialytic intercurrences consisted ofvomiting in 16 sessions (22.22%), hypotension in 11 sessions(15.27%) and the need to change the double lumen catheterin 4 sessions (5.55%). Three animals (37.5%) had neurologicalchanges such misorientation, vocalizations or convulsion(dialysis disequilibrium syndrome) soon after the end of IHD.

Hypotension was recorded in 11 sessions, generallybetween 10 and 25 min at the beginning of IHD session, withvery good responses to fluid therapy IV, with an isotonic salinesolution, alone or with mannitol, with normal average values

of SAP at the end of IHD sessions (Table 1). Four sessions hadthe catheters damaged or obstructed during IHD and 3 ofthese catheters were replaced in the initial puncture site witha guidewire. The use of a new puncture site in thecontralateral external jugular vein was necessary in onesession.

The daily mean values obtained with evaluation of HR andRR did not reveal significant differences among T0, T5, T30 andT60 at different time points. Although, FC was significantlyincreased at M9, when compared to other moments (p<0.05),the mean values were normal at each of the other analyzedtimes, while RR showed an unremarkable taquipnea in M3(T3 and T 60), M5 (T60) and M9 (T 30 and T60) (Table 1).

The rectal temperature fell when compared to T0, whichwas significant in different moments (p< 0.05). Mean valuescorresponding to hypothermia were noted in M1 (T0, T5 andT30), M3 (T5), M7 (T30 and T60) and M9 (T5, T30 and T60)(Table 1).

A significant reduction in post-dialytic period was seen inHct (M3, M4, M8 and M9) (p<0.05), in platelet counts (all themoments) (p<0.05) and in WBC (M2 to M6 and M9) (p<0.05),when compared to pre-dialytic period (Table 2).

Table 1: Clinical parameters evaluated in dogs with acute renal failure submitted to daily hemodialysis sessions (60 min) for a period of 9 days (M1-M9)M1 M2 M3 M4 M5 M6 M7 M8 M9

Heart rate (bpm)0 min 93.5±20.6* 106.0±24.0* 86.5±15.7* 80.0±17.0* 88.5±24.7 91.0±12.1 108.0±28.0 103.3±39.2 133.5±33.15 min 118.5±40.2 96.5±17.3 92.5±21.1 81.0±18.2* 93.0±26.0 93.5±28.4 103.5±24.0 109.0±31.0 124.0±26.530 min 92.5±11.0 82.5±8.8 91.0±17.7 74.0±16.1* 77.8±34.6 92.5±36.0 92.5±22.9 116.0±53.6 117.0±35.960 min 92.0±16.1* 97.3±45.2* 85.3±25.1* 76.8±17.4* 88.0±34.1* 91.5±29.8* 111.0±43.6* 114.0±42.1* 150.5±52.5Respiratory rate (rpm)0 min 22.5±6.4 24.5±9.9 19.0±2.0 21.5±3.1 24.0±3.4 19.5±2.2 27.5±14.4 26.8±14.6 29.0±15.85 min 21.5±6.7 23.5±11.8 22.0±10.5 27.5±28.1 22.5±8.0 19.5±4.5 26.5±13.9 29.0±18.4 27.5±17.930 min 23.3±7.7 28.5±17.4 46.5±66.6 29.5±28.9 21.5±11.3 16.0±6.8 23.3±11.8 30.5±17.4 36.0±29.260 min 25.0±11.7 23.5±12.2 42.0±64.0 30.5±28.9 36.0±37.2 21.5±10.2 23.5±10.4 29.0±17.7 47.0±40.8‡

Rectal temperature (EC)0 min 37.7±0.6 38.1±0.2 37.9±0.5 38.1±0.5 38.2±0.4 38.0±0.6 38.0±0.7 38.0±0.7 37.9±1.35 min 37.6±0.6 38.0±0.4 37.7±0.5 37.9±0.5 38.0±0.3 37.9±0.6 37.9±0.6 38.0±0.7 37.7±1.330 min 37.7±0.6 38.0±0.3 37.9±0.4 38.0±0.4 38.0±0.3 37.8±0.3† 37.7±0.5 37.9±0.6 37.7±0.960 min 37.9±0.6 37.9±0.2† 37.8±0.5 37.9±0.4† 37.8±0.3 37.8±0.3 37.7±0.5 37.9±0.5 37.7±0.9Systolic arterial pressure (mmHg)0 min 153.8±37.8 181.3±36.8§ 172.5±40.6 175.0±40.4 170.0±42.4 158.3±54.6 160.3±34.2 155.6±43.4 148.8±64.55 min 147.5±34.9 160.0±31.6 156.3±43.7 158.8±28.5 161.3±34.0 157.5±56.5 151.5±44.7 148.5±55.7 128.8±73.460 min 155.0±38.5 163.5±35.9 157.5±48.3 173.8±38.5 159.5±35.9 173.0±53.6 161.8±45.2 141.9±52.0 140.3±54.6*p<0.05×M9, †p<0.05×T0; ‡p<0.05×T5, §p<0.05×T60, M: moments, values are Mean±SD

Table 2: Hematological parameters evaluated in ARF dogs submitted to IHD, at different times after (Tpre) and before (Tpos) IHD sessionsM1 M2 M3 M4 M5 M6 M7 M8 M9

Hematocrit (%)TPre 32.50±5.3 31.00±6.2 28.80±6.5* 28.90±6.4* 27.90±7.4 28.20±7.3 27.70±7.3 27.50±7.7* 26.4±9.7*TPos 31.60±7.1 29.10±6.8 26.10±5.7 27.40±8.6 28.20±9.8 26.90±8.2 27.40±9.8 23.80±9.5 22.3±9.7White blood count (×103 mmG3)TPre 8.58±3.15 8.54±2.14* 8.64±3.15* 7.93±2.06* 9.85±3.19* 10.04±2.9* 11.25±6.91 11.36±6.47 14.44±8.31*TPos 8.16±4.57 7.04±2.60 7.50±3.06 6.90±2.39 8.46±2.98 8.61± 3.65 10.59±4.33 9.73±4.25 10.79±5.86Platelets count (×103 mmG3)TPre 116.80±38.9* 97.30±25.6* 99.30±41.4* 107.40±40.8* 117.90±46.0* 91.60±33.3* 98.70±48.6* 103.00±51.7* 95.00±64.2*TPos 79.00±33.3 62.30±25.1 76.60±40.7 73.10±27.2 81.80±35.6 69.80±26.4 88.00±46.0 76.10±45.5 65.00±55.8*p<0.05×TPos, values are Mean±SD

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DISCUSSION

A prescript schedule was associated with a low incidenceof dialysis complications or relevant changes in vitalparameters. Several complications during the intradialyticperiod were determined to be transitory, includinghypotension, vomiting, neurological changes, blood loss,neutropenia and problems with vascular access1. These resultswere supported by this study.

Hypotension is the most important complication duringIHD and often requires premature termination of sessions ofIHD11. Hypotension may be caused by the removal of bloodvolume from the patient at the beginning of extracorporealcirculation, especially in animals with small body mass2 and itis unlikely in this study, once hypotension episodes occurredmainly after 10 min in IHD session, probably due primingwhich was infused at the beginning of IHD session. Theexposure of blood to the membrane of the dialysis machinemay induce the release of cytokines and others inflammatorymediators, resulting in hypotension11,12 and it is likely in thisstudy.

The occurrence of hypotension in this study, observed in15.27% of IHD sessions, was easily corrected by an IV isotonicsaline solution, isolated or combined with mannitol. Thecorrection of hypotension was improved by normal levels ofSAP at the end of IHD sessions. Shorter durations of IHD, aswell its circuit connection with a priming solution, probablyresulted in the low occurrence of hypotension and helped toeasily correct it.

Vomiting was the most prevalent change in this study,mainly observed in the first 30 min of IHD. Other authors alsodescribed vomiting as usual occurrence at the beginning of IHD, due to hypotension, deviation of blood flow from thegastro-intestinal tract or reactions with hemodialyzermembranes1.

The choice of vascular access with double-lumen catheterwas adequate for the IHD performance, since the loss of accessoccurred in a reduced number of sessions (5.55%). The loss ofaccess in the present study occurred due to physicalobstruction by clots and adherence of fibrin (in 3 sessions) orkinking (in 1 session) of the catheters. The placement oftemporary double-lumen catheter in the central vein is afavorable choice in dogs, since the implantation is quickly andpractical1. In addition, there is the possibility of immediate useand low venous resistance to blood circulation8.

The dysfunctions in vascular access are related todysfunctions in the double-lumen catheter, caused by physical

obstructions such as clots and adherence to fibrin (75%) orbending (25%)1,13, which were supported by the present study.Polyurethane catheters used for temporary vascular access areless flexible and are prone physical damage and kinking14.

Once the catheter thrombosis impedes extracorporealblood flow, it reduces the adequacy of dialysis8,15 and increasesthe risk of infections16,17. This occurrence requires thechanging of the dialyses catheter8, which may be done withwire guides without requiring an additional vein for itsimplantation1. In the present study, catheters werereplaced in the same site of the initial puncture in 3 sessionsand only in 1 session the catheter removal-replacement wasat a new site.

Dialysis disequilibrium was a syndrome induced by rapiddialysis in severely azotemic patients, caused by changes inblood composition. The pathogenesis involves the removal ofurea from the blood compartment faster than the rate ofdiffusion from intracellular compartments to blood, resultingin an osmotic gradient that causes brain intracellular edema.The signals may include agitation, disorientation, convulsionsand coma or death12.

Some neurological changes, such as misorientation,vocalizations or convulsions were observed soon after the endof IHD in this study, despite the low extracorporeal blood flowused at the beginning of the IHD sessions and short durationsessions. However, these changes were transitory andresponded well to therapy. The neurological changesobserved in dogs with ARF subject to IHD, may be due touremic consequences, or due to the dialysis procedure itself8.

Hematological complications include frequentthrombocytopenia and leukopenia at the end of IHD13,18.Thrombocytopenia is an adverse reaction, which is commonin patients on heparin therapy19. It is commonly type I, whichis transitory and benign and caused by platelet aggregationinduced by heparin. It is rarely associated with bleeding orthromboembolic sequels20 and it is likely what was observedin this study. Type II thrombocytopenia occurs byimmunoallergic reactions21 caused by IgG, IgM and IgAagglutination to platelets and is often associated withthromboembolic complications18.

The occurrence of leukopenia was observed after IHD.Intense but reversible leukopenia has been reported and it isconsidered a collateral effect of IHD treatment8. Leukopenia iscaused by the migration of neutrophils to the pulmonarybed22-24, due to the activation of the complement systemwhen blood comes into contact with the hemodialyzermembrane22.

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Sequestration of neutrophils in pulmonary capillariesinterferes with oxygen diffusion and results in thedevelopment of hypoxemia, generally within 30-60 min of thestart of dialysis. This may be an explication to taquipneaobserved in T30 and T60, since hypoxic dogs have anincreased respiratory rate25.

A significant decrease of hematocrit was observed inpost-dialytic period as a possible consequence of blood lossduring the procedure. Furthermore, the addition of anisotonic saline solution at the end of the procedure andduring hypotensive episodes, hemorrhage due to uremicthrombocytopathy or gastro-intestinal ulceration andrepeated blood sampling may contribute to a reduction inhematocrit26.

In the last decades the prevalence of renal disease hasincreased significantly and hemodialysis is an importantmodality for renal replace therapy. The present datademonstrated the hemodialysis complications in dogs withacute renal failure. Despite this technique is associated withseveral side effects, this study demonstrated that theshort-duration daily hemodialysis sessions in dogs withacute renal failure is associated with a low incidence ofcomplications. However, this study evaluated only animalssubmitted to the same hemodialysis protocol. It should beconsidered that some complications may be related to aspecific protocol, which is a limitation of the study.

CONCLUSION

Daily short-session hemodialysis is a safe therapyassociated with a small occurrence of complications in dogs.The complications were easily corrected and includedhypotension, problems with vascular access, neurologic,respiratory, hematologic and gastrointestinal alterations.

SIGNIFICANCE STATEMENTS

This study discovers a low incidence of hemodialysiscomplications that can be beneficial for dogs with acute renalfailure. This study will help the researcher to uncover thecritical areas of renal replacement therapy complications thatmany researchers were not able to explore. Thus, a new theoryon the use of short-term daily sessions of hemodialysis may befeasible for patients with severely impaired renal function.

ACKNOWLEDGMENT

This study (process 160/2000) was supported by theHemodialysis Center of the Botucatu Medical School,Universidade Estadual Paulista (Unesp), Botucatu city, Brazil.

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