No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Treatment of meloxicam overdose in a dog via therapeutic plasma exchange
Journal of Veterinary Emergency and Critical Care
Abstract
Objective:
To describe the treatment of a meloxicam overdose in a dog with therapeutic plasma exchange (TPE).
Case summary:
A 6-month-old female Bulldog, presented for routine laparoscopic ovariectomy. Postoperatively the dog received an accidental overdose of meloxicam (1 mg/kg IV [intravenously]). The patient was treated with supportive medical therapy and TPE over 210 minutes achieving 1.2 plasma volume exchanges. During therapy, heparinized blood and effluent samples were collected. Meloxicam concentrations were determined in the samples by high pressure liquid chromatography. Post TPE, the dog continued to receive supportive medical therapy and was discharged 48 hours after the overdose. The dog remained asymptomatic for meloxicam intoxication. Follow-up rechecks at 1 and 6 weeks were unremarkable with no further treatment required.
New or unique information:
This report describes the successful use of TPE adjunctively following an acute meloxicam overdose. An 82% reduction of plasma meloxicam concentration was achieved over 210 minutes. Twenty-four hours after therapy, a 47% sustained reduction of plasma meloxicam was measured after redistribution of drug between body compartments.
... Recently, extracorporeal blood purification (ECBP) therapies have gained popularity in the treatment of NSAID toxicities in companion animals with successful mitigation of the effects of severe toxicoses (4,5,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Therapeutic plasma exchange (TPE) has been reported to reduce plasma NSAID levels by 51-85.5% after a single session (9,10,(12)(13)(14). ...
... Recently, extracorporeal blood purification (ECBP) therapies have gained popularity in the treatment of NSAID toxicities in companion animals with successful mitigation of the effects of severe toxicoses (4,5,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Therapeutic plasma exchange (TPE) has been reported to reduce plasma NSAID levels by 51-85.5% after a single session (9,10,(12)(13)(14). Hemoperfusion has been less commonly reported in small animals but has successfully reduced plasma NSAID levels by 37-79%; all previous reports used an intermittent hemodialysis platform with an in-series dialyzer and older charcoal sorbents (15,16). ...
... Both animals presented here were concurrently treated with standard medical management (IV fluids, gastric acid reducers, and GI protectants) as is standard practice when ECBP techniques are utilized to treat NSAID toxicity (4,5,(8)(9)(10)(11)(12)(13)(14)(15)(16). No clinical signs of NSAID overdose, such as GI hemorrhage or acute kidney injury, were noted in either pet, although the relative contributions of MCHP versus standard medical management to the mitigation of clinical signs of toxicosis are unknown. ...
Extracorporeal blood purification (ECBP) has become a popular treatment option for non-steroidal anti-inflammatory drug (NSAID) toxicity in small animals. However, challenges arise when using ECBP for small dogs and cats because the priming volume required by most machine-based ECBP platforms might be excessive, leading to cardiovascular instability if a blood prime is not used. This report describes the successful use of manual carbon hemoperfusion (MCHP) to reduce plasma meloxicam levels in a cat following an inadvertent overdose and its use in a dog following suspected ibuprofen ingestion. In both animals, MCHP reduced the circuit volume needed for ECBP from 125 mL with a machine-based therapeutic plasma exchange or 104 mL with an in-series carbon hemoperfusion on an intermittent hemodialysis platform to just 40–50 mL. In the cat, MCHP reduced plasma meloxicam levels by 44%, and in both animals, the use of MCHP in these pets was well-tolerated and safe. Due to pre-existing anemia, the cat required a blood transfusion but the dog did not. MCHP is technically simple and can be performed at any hospital with access to carbon filters and blood bank resources. This technique may represent a reasonable alternative to treat NSAID toxicities in animals that are too small for conventional extracorporeal decontamination methods using either machine-based platforms without using a blood prime or in locations where these machines are unavailable.
... 8,17,18 Given the high frequency of ingestion of nephrotoxic drugs and the expense of multiple days of treatment with fluid diuresis and supportive care in the hospital, EBP appears to be an attractive alternative to clear toxins and prevent subsequent organ dysfunction. Although there are a handful of veterinary case studies showing the utility of EBP in removal of exogenous toxins, 13,[19][20][21][22][23][24] to the authors' knowledge, there is a lack of published information in veterinary medicine regarding the general use of EBP in acute toxin exposure and the outcome and complications associated with these therapies. ...
... 8 Although several veterinary case reports have quantified the removal of a toxin from plasma, the percentage of removal does not necessarily correlate with improved outcome. 13,[19][20][21][22][23][24] This is because the toxin at the action site cannot be measured, and endogenous clearance has not been accounted for in many cases. In theory, the sooner that EBP is initiated before a toxin can be distributed out of the blood to vital organs, the more beneficial this therapy will be. ...
... Recommended therapeutic doses based available on veterinary pharmacology resources.35 highly protein bound.21,22 Although HD + HP could have been used to remove NSAIDs, TPE does not frequently cause thrombocytopenia and leukopenia, as reported with the use of HP filters.13,14 ...
Objective
To investigate the clinical outcome and complications associated with extracorporeal blood purification (EBP) using either hemodialysis (HD), hemodialysis and hemoperfusion (HD + HP), or therapeutic plasma exchange (TPE) for the management of acute toxin ingestion in small animals.
Design
Retrospective, multicenter study from January 2011 to July 2018.
Setting
One university teaching hospital and one private specialty hospital.
Animals
Fifty‐one dogs and 3 cats with a history of acute toxin exposure that could lead to severe morbidity and mortality, managed with different EBP techniques.
Main Results
Nonsteroidal anti‐inflammatory drugs (38/54, 52%), baclofen (8/54, 15%), and ethylene glycol (7/54, 13%) were the most common toxicities treated with EBP. Membrane‐based TPE was used most commonly (22/54, 40.7%), followed by HD (17/54, 31.5%) and then HD + HP (15/54, 27.8%). There was an 83.3% (45/54) overall survival, with 88.9% (8/9) of nonsurvivors having clinical signs prior to therapy. One third (18/54) of the patients never developed clinical signs of toxicity. Treatment complications occurred in 44.4% (24/54) of the animals, although only 18.5% (10/54) of these complications, such as mild hypotension, thrombocytopenia secondary to the HP cartridge, facial swelling after plasma transfusion for TPE, bleeding from catheter size secondary to heparinization, or clotting of the system, could be attributed to the EBP treatment. None of the nonsurvivors died because of EBP complications.
Conclusions
Early initiation of EBP therapy might be considered as an alternative route of decontamination in severe acute toxicities with high potential for significant morbidity and mortality. The survival rate in small animals undergoing EBP is high despite exposure to potential lethal doses of toxins, and survival appears to be more likely if clinical signs of toxicity are not present at the time of EBP. Continued research is warranted with randomized controlled clinical trials to further evaluate the clinical efficacy and benefit of EBP.
... Plasmapheresis has been performed in veterinary medicine since in the 1980s and remains relevant today for a variety of conditions such as immunologic diseases, [3][4][5][6][7] Ehrlichia canis infection, 8 kernicterus, 9 and multiple myeloma. 10 Recently, 3 case reports have described the use of TPE for ibuprofen, 11 meloxicam, 12 and carprofen 13 overdose. ...
... Although TPE is not a new technique in veterinary medicine, with multiple reports of its use in the 1980s, 3,4,7,8,29 there are few reports of its use for toxicity cases. In the past 2 years, 3 case reports of the use of TPE for NSAID overdose have been published for ingestions of meloxicam, 12 ibuprofen, 11 and carprofen. 13 Although all these were single case reports, the results were promising, with good clinical outcomes and evidence of an 82% reduction in plasma meloxicam concentrations, 12 an 85% reduction in plasma ibuprofen concentrations, 11 and a 51% decrease in plasma carprofen concentrations. ...
... In the past 2 years, 3 case reports of the use of TPE for NSAID overdose have been published for ingestions of meloxicam, 12 ibuprofen, 11 and carprofen. 13 Although all these were single case reports, the results were promising, with good clinical outcomes and evidence of an 82% reduction in plasma meloxicam concentrations, 12 an 85% reduction in plasma ibuprofen concentrations, 11 and a 51% decrease in plasma carprofen concentrations. 13 A limitation of our study is that plasma concentrations of the NSAIDs were not measured, and it is impossible to say how much of a decrease was achieved. ...
Background
Therapeutic plasma exchange (TPE) may be an effective technique for treatment of accidental nonsteroidal anti‐inflammatory drug (NSAID) overdose, but information regarding the use of this technique in veterinary medicine is currently limited.
Objectives
To evaluate the overall outcome for dogs with NSAID overdose treated with TPE and to determine if any presenting factors can predict or influence overall outcome. Secondary objectives included investigating TPE complications as well as the utility of other adjunctive treatments.
Animals
Eleven client‐owned dogs presented for NSAID overdose that received TPE. All patients also received additional supportive treatment including IV lipid infusion.
Methods
Retrospective review of medical records.
Results
Eleven cases were included in the study. Of these, the NSAID ingested was ibuprofen in 6 (54.5%), naproxen in 4 (36.4%), and deracoxib in 1 (9.1%). All dogs survived to discharge with 3 (27.3%) developing acute kidney injury during hospitalization. A larger initial dose of NSAID ingested was associated with a higher maximum serum creatinine concentration during hospitalization (P = .04) and larger change in serum creatinine concentration from baseline (P = .02). Six dogs (54.5%) developed complications associated with TPE. The use of other treatments did not affect the overall outcome.
Conclusions and Clinical Importance
We identified TPE as an effective treatment for NSAID overdose with good outcomes despite high doses of NSAID ingestion in dogs treated with a single TPE treatment. Complications were common but did not affect the final outcome. Therapeutic plasma exchange should be considered in patients presenting for high‐dose NSAID ingestion.
... µg/mL. This occurred at 23.74 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) h. The geometric mean terminal elimination half-life in milk was 12.23 (10.59-14.4) ...
... Multiple dosing regimens have been used to evaluate the toxic effects of high doses of meloxicam in laboratory animals, with most utilizing daily doses over time. There is one report of a dog accidentally receiving 1 mg/kg IV (intravenously) meloxicam where therapeutic plasma exchange was successfully employed to circumvent any toxicologic effects, so it is unknown if this dose would have resulted in any adverse effects in a dog [30]. Severe clinical signs and lesions occurred in a study using Wistar rats where the rats were orally gavaged with 8 mg/kg meloxicam for 28 days. ...
Adverse effects associated with overdose of NSAIDs are rarely reported in cattle, and the risk level is unknown. If high doses of NSAIDs can be safely administered to cattle, this may provide a longer duration of analgesia than using current doses where repeated administration is not practical. Meloxicam was administered to 5 mid-lactation Holstein dairy cows orally at 30 mg/kg, which is 30 times higher than the recommended 1 mg/kg oral dose. Plasma and milk meloxicam concentrations were determined using high-pressure liquid chromatography with mass spectroscopy (HPLC-MS). Pharmacokinetic analysis was performed by using noncompartmental analysis. The geometric mean maximum plasma concentration (Cmax) was 91.06 µg/mL at 19.71 h (Tmax), and the terminal elimination half-life (T1/2) was 13.79 h. The geometric mean maximum milk concentration was 33.43 µg/mL at 23.74 h, with a terminal elimination half-life of 12.23 h. A thorough investigation into the potential adverse effects of a meloxicam overdose was performed, with no significant abnormalities reported. The cows were humanely euthanized at 10 d after the treatment, and no gross or histologic lesions were identified. As expected, significantly higher plasma and milk concentrations were attained after the administration of 30 mg/kg meloxicam with similar half-lives to previously published reports. However, no identifiable adverse effects were observed with a drug dose 30 times greater than the industry uses within 10 days of treatment. More research is needed to determine the tissue withdrawal period, safety, and efficacy of meloxicam after a dose of this magnitude in dairy cattle.
... In small animal medicine and occasionally, smaller-sized large animals, intravenous administration of lipid emulsion (ILE) has become an adjunct therapy in NSAID toxicosis [5][6][7][8] with increasing use of extracorporeal blood purification strategies. [9][10][11][12] In addition to being a component of parenteral nutrition, ILE is used in both human and veterinary medicine as an antidote in Abbreviations: ACT, activated clotting time; cTPE, centrifuge-based therapeutic plasma exchange; HES, hydroxyethyl starch; ILE, intravenous administration of lipid emulsion; mTPE, membrane-based therapeutic plasma exchange; NSAID, nonsteroidal anti-inflammatory drug; Qb, blood flow; RCA, regional citrate anticoagulation; TPE, therapeutic plasma exchange; TS, total solid; UFH, unfractionated heparin. toxicoses associated with the overdose of lipophilic compounds, such as tricyclic antidepressants, calcium-channel blockers, β-blockers, macrocyclic lactone anthelmintics, and, more recently, NSAIDs. ...
... This formulation of replacement fluid has been successfully used in dogs. [9][10][11][12]17 Fresh plasma was collected from donor goats in the insti- The session was initiated 4 hours after the overdose had occurred. The goat's ACT prior to the mTPE was 99 seconds (reference interval: 91 ± 3 seconds) and served as a baseline measurement. ...
A 12 week‐old Nigerian dwarf (Capra aegagrus hircus) buck kid was hospitalized for management of obstructive urolithiasis. Postoperatively, he was inadvertently administered 16‐times greater than his calculated dose of a nonsteroidal anti‐inflammatory drug (NSAID; 17.5 mg/kg flunixin meglumine, IV). The goat was treated with intravenous administration of lipid emulsion (ILE) prior to membrane‐based therapeutic plasma exchange (mTPE) under general anesthesia. The increased coagulability inherent to small ruminants in comparison with dogs and cats warranted specific adjustments in the prescription of anticoagulation, blood flow, and filtration fraction to avoid circuit clotting during mTPE. Serum flunixin meglumine concentration measured before, during, and after mTPE revealed marked reduction in drug concentration. After the combined treatments, no clinical evidence of NSAID gastrointestinal or renal toxicosis was detected. This case report describes successful management of flunixin meglumine overdose in a small ruminant using combined ILE and mTPE.
... [10][11][12] Recently, both the veterinary and human fields have found success in treating drug overdoses with TPE, specifically ibuprofen, meloxicam, and carprofen. [13][14][15][16] TPE is most efficient at removing highly protein-bound drugs (>80% protein binding), with a low volume of distribution (ie, <0.2 L/kg). 7,12-14 ...
... Based on current guidelines, a 1.5 plasma volume exchange aims to remove 78% of the target substance while a 2.0 plasma volume exchange only removes 86% (8% increase), which is considered clinically irrelevant, this has been observed in other cases of NSAID removal with TPE. [14][15][16] This case report demonstrates that TPE in combination with oral administration of activated charcoal and additional supportive care can be effective in the treatment of high doses of naproxen ingestion. ...
In comparison with other over‐the‐counter anti‐inflammatory drugs, naproxen has a longer half‐life in dogs and can lead to severe morbidity and mortality. This report describes the successful use of membrane‐based therapeutic plasma exchange after a massive ingestion of naproxen by a dog resulting in 86% reduction in plasma concentration. In comparison with other over‐the‐counter anti‐inflammatory drugs, naproxen has a longer half‐life in dogs and can lead to severe morbidity and mortality. This report describes the successful use of membrane‐based therapeutic plasma exchange after a massive ingestion of naproxen by a dog resulting in 86% reduction in plasma concentration.
... The clinical use of PEX in dogs has been previously described in several conditions such as systemic lupus erythematosus (12), hyperviscosity syndrome (13,14), myasthenia gravis (15), immune-mediated hemolytic anemia (16), treatment of meloxicam and ibuprofen overdose (17,18), and kernicterus (19). The management of patients with clinically suspected CRGV in the UK has been challenging given that there is no known underlying etiology and there is severe morbidity associated with the condition. ...
... The complications associated with PEX observed in the current study are similar to those previously reported, such as hypotension and citrate-induced hypocalcemia (12)(13)(14)(15)(16)(17)(18). Other complications of extracorporeal therapies previously reported such as hypersensitivity reaction to replacement fluids (16) were not observed in our study. ...
Cutaneous and renal glomerular vasculopathy (CRGV) is a rare disease affecting dogs, with a recent apparent increase in prevalence since 2012 in the UK. This disease is characterized by a vasculopathy affecting small vessels of the kidney and skin, leading to thrombotic microangiopathy. The underlying etiology remains unknown although clinicopathological and histological findings resemble features of certain forms of thrombotic microangiopathy in people, for which plasma exchange (PEX) is considered an important component of therapy. The objective of the present study is to describe the use of PEX as adjunctive treatment in dogs diagnosed with CRGV. A retrospective review of dogs diagnosed with CRGV between 2014 and 2016 treated with PEX was performed. Clinical records were reviewed and data relating to signalment, diagnostic tests and management strategies were summarized. Information and complications relating to PEX were recorded. Six dogs were diagnosed with CRGV (n = 2 ante-mortem, n = 4 post-mortem) and underwent PEX as part of their therapy. All dogs had cutaneous lesions and were azotemic with oliguria or anuria. All dogs underwent at least one PEX cycle; one dog had a single cycle PEX, three dogs two cycles PEX, and two dogs had one cycle PEX and one cycle of prolonged intermittent renal replacement treatment. Complications seen during PEX therapy included hypothermia (n = 4), tachycardia (n = 2), hypotension (n = 2), and hypocalcemia (n = 6). Two dogs survived to discharge, the remaining four dogs were euthanized. The positive outcome in two dogs treated with PEX despite the reported high mortality rate once acute kidney injury with oliguria/anuria occurs does not confirm success of this treatment. However, survival in two dogs that were initially oligoanuric highlights that further consideration and evaluation of PEX for this patient group is warranted for this specific disease. Additional studies are urgently needed to identify the underlying etiology of CRGV before more targeted therapies can be developed. Based on our findings, further evaluation of the role of PEX in this specific disease are warranted.
... The system also features a temperature controller and a cooling plate to keep the acoustofluidic chip at the optimal temperature, preserving blood integrity during extracorporeal circulation. Due to the small size of the microfluidic channels and interconnecting tubing, the entire system boasts an extracorporeal volume of just 280 μL. Figure 1e contrasts the ATAS with other apheresis systems for animals found in the literature, including those by Ma et al. 17 , Francy et al. 44 , Walton et al. 45 , and Ahmed et al. 46 . The ATAS stands out as the only system with an extracorporeal volume well below the dangerous blood loss threshold for mice (approximately 0.4 mL). ...
Therapeutic apheresis aims to selectively remove pathogenic substances, such as antibodies that trigger various symptoms and diseases. Unfortunately, current apheresis devices cannot handle small blood volumes in infants or small animals, hindering the testing of animal model advancements. This limitation restricts our ability to provide treatment options for particularly susceptible infants and children with limited therapeutic alternatives. Here, we report our solution to these challenges through an acoustofluidic-based therapeutic apheresis system designed for processing small blood volumes. Our design integrates an acoustofluidic device with a fluidic stabilizer array on a chip, separating blood components from minimal extracorporeal volumes. We carried out plasma apheresis in mouse models, each with a blood volume of just 280 μL. Additionally, we achieved successful plasmapheresis in a sensitized mouse, significantly lowering preformed donor-specific antibodies and enabling desensitization in a transplantation model. Our system offers a new solution for small-sized subjects, filling a critical gap in existing technologies and providing potential benefits for a wide range of patients.
... [10][11][12][13] Therapeutic plasma exchange (TPE) has also become more commonly used in the management of NSAID intoxications in dogs. [14][15][16][17][18][19] This technique involves the separation of the cellular components of blood from plasma by either centrifugal or membrane-based TPE, facilitated by either the rotation of a blood chamber or a nonselective membrane filter, respectively. 20 This technique allows for high amounts of protein-bound toxins to be removed from the circulation and replaced with donor plasma, preventing potentially life-threatening consequences associated with NSAID intoxication. ...
Background
Traditional management of non‐steroidal anti‐inflammatory drug (NSAID) intoxication includes gastrointestinal decontamination, intravenous administration of fluids (IVF), and gastroprotection. Intravenous administration of lipid emulsion (ILE) and therapeutic plasma exchange (TPE) are popular novel therapeutic strategies.
Hypothesis
Compare outcomes of dogs treated with IVF, ILE, and TPE for NSAID intoxications and evaluate outcome predictors for drug subgroups.
Animals
Four hundred thirty‐four dogs with NSAID intoxications (2015‐2020).
Methods
Multicenter retrospective study of ibuprofen, carprofen, and naproxen intoxication. An ordinal outcome was defined as mild gastrointestinal, moderate kidney, or signs of severe central nervous system disease.
Results
Signs of neurological disease were overrepresented and acute kidney injury underrepresented in the TPE group among dogs exposed to kidney‐ or CNS‐toxic doses (P = .05), though all TPE dogs with signs of neurological disease had evidence of neurotoxicity at presentation. Dogs treated with IVF had a higher maximal creatinine concentration (median, 1.1 mg/dL; range, 0.4‐8.44 mg/dL) compared with IVF + ILE (median, 0.9 mg/dL; range, 0.4‐6.2 mg/dL; P = .01). Increased maximum time to presentation (P < .001), higher baseline creatinine (P < .001) and PCV (P = .007), and absence of induced emesis (P < .001) were associated with greater clinical severity. Ibuprofen toxicosis was associated with more severe clinical signs compared with carprofen (P = .03). Overall survival rate was 99%.
Conclusions and Clinical Importance
NSAID toxicosis generally carries an excellent prognosis in dogs. Despite similar outcomes of lower incidence of AKI in the TPE group, and slightly lower maximal creatinine concentration in dogs treated with ILE vs IVF alone, ILE and TPE should be considered in the management of severe NSAID toxicosis.
... 4,8,9 Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique that has gained popularity as a management option for NSAID intoxications. [10][11][12][13][14] The pharmacokinetic characteristics of NSAIDs are well suited to clearance by TPE because they have small molecular weights (206. .71 ...
Background
Therapeutic plasma exchange (TPE) is gaining popularity for the management of nonsteroidal anti‐inflammatory drug (NSAID) overdose in dogs.
Hypothesis/Objectives
Describe a population of dogs treated with TPE for NSAID overdose.
Animals
Sixty‐two dogs with NSAID overdose treated with TPE.
Methods
Multicenter retrospective study of dogs treated with TPE for ibuprofen, carprofen, or naproxen overdose.
Results
The median dose of ibuprofen, carprofen or naproxen ingested was 533 mg/kg (range, 36‐4857 mg/kg), 217 mg/kg (range, 88‐625 mg/kg) and 138 mg/kg (range, 26‐3000 mg/kg), respectively. Based on previously established toxic ranges for each NSAID, 2 (3.2%), 14 (22.6%), and 46 (74.2%) dogs ingested a gastrointestinal, renal, and neurological toxic dose, respectively. The median time between ingestion and presentation was 4 hours (range, 1‐20 hours). The median number of plasma volumes processed was 1.6 (range, 0.4‐2.2). The median TPE session duration was 2 hours (range, 1‐4.5 hours). Circuit clotting developed during 8 (12.9%) sessions. Patient adverse events reported during 21 (33.8%) sessions consisted of urticaria (12.9%), asymptomatic hypocalcemia (9.6%), and hypotension (9.6%). The median duration of hospitalization was 2.25 days (range, 1‐11 days). Sixty‐one (98.4%) dogs survived to discharge, and none were rehospitalized. Thirty‐one (91.1%) of the 34 dogs with at least 1 follow‐up visit were not azotemic at the time of reevaluation.
Conclusions and Clinical Importance
This population of dogs managed with TPE had excellent outcomes, even in cases of high NSAID dose ingestion. When TPE is available and the time frame is appropriate, this extracorporeal modality should be considered for the management of NSAID overdose.
... No studies have reported TPE for chemotherapy ODs in veterinary medicine, but several case reports describe its use for nonsteroidal anti-inflammatory drug toxicities. 26,27 In humans, TPE has been successful for accidental ODs of highly protein-bound chemotherapeutic agents such as vincristine, vinblastine, and cisplatin. 28,29 Although both DOX and MTX are highly protein bound, 30,31 the volume of distribution also is high: between 2.2 and 7.8 L/kg for DOX 32 and 26.6 ± 4.9 L/kg for MTX. ...
Background
Despite multiple reports of chemotherapy overdoses (ODs) in human and veterinary medicine, anthracycline ODs have been described infrequently.
Hypothesis/Objectives
Describe toxicities, treatments, and overall outcome after anthracycline OD in dogs.
Animals
Twelve mitoxantrone (MTX) and 4 doxorubicin (DOX) ODs were evaluated.
Methods
Multicenter retrospective analysis. The American College of Veterinary Internal Medicine oncology and internal medicine listservs were solicited for cases in which a chemotherapy OD occurred.
Results
Sixteen anthracycline cases were collected. Anthracycline ODs occurred because of an error in chemotherapy preparation (n = 9), or dose miscalculation (n = 7). The overall median OD was 1.9× (range, 1.4‐10×) the prescribed amount. Most ODs were identified immediately after drug administration (n = 11), and the majority of patients were hospitalized on supportive care (n = 11) for an average of 8 days (range, 3‐34 days). Adverse events after the OD included neutropenia (94%), thrombocytopenia (88%), anemia (63%), diarrhea (63%), anorexia (56%), vomiting (38%), lethargy (31%), and nausea (25%). Two patients did not survive the OD. High grade neutropenia was common and did not appear to be mitigated by the administration of filgrastim.
Conclusions and Clinical Importance
All patients received supportive care after identifying the OD and death was uncommon. Further evaluation is needed to determine ideal therapeutic guidelines anthracycline OD.
... 7 In the veterinary literature, there are few case reports describing the use of TPE used to treat nonsteroidal anti-inflammatory drug toxicity and hyperbilirubinemia. [8][9][10][11][12] The use of TPE to remove antibodies has also been described in dogs with immune-mediated hemolytic anemia. 13 This case series describes 3 cases of suspected acquired MG in dogs that were treated with membrane-based TPE. ...
Objective
To describe the use of therapeutic membrane‐based plasma exchange (TPE) for treatment of clinical signs associated with suspected acquired myasthenia gravis (MG) in 3 dogs.
Case series summary
Three dogs presented with clinical signs consistent with acquired MG. All 3 dogs were medically managed prior to being treated with TPE. Two of the 3 dogs had increased acetylcholine receptor antibody titers that decreased after TPE. One dog diagnosed with primary MG became clinically normal after 2 sessions of TPE and continued to do well with medical management several months later. The second dog was diagnosed with a suspect thymoma, and TPE was performed as a bridge to surgery, with marked improvement of clinical signs after TPE. The dog was ultimately diagnosed with a thymic carcinoma. The third dog had a positive acetylcholine antibody titer and was ultimately diagnosed with hemangiosarcoma (spleen and liver) and invasive mediastinal thymoma. This dog developed severe pneumonia, was ventilator dependent, and died of multiple organ dysfunction. No immediate complications were observed secondary to TPE. All 3 dogs were concurrently treated with either immunosuppressive agents, anticholinesterase drugs, or both.
New or unique information provided
The use of TPE in dogs with MG appears to be well tolerated and safe. It may be a reasonable adjunct therapy to acetylcholinesterase drugs in cases that are not responding to medical management alone. Therapeutic plasma exchange might also be considered preoperatively to prevent postoperative complications in dogs with severe MG, although further studies should be performed.
... Considering the pharmacological properties of carprofen, therapeutic plasmapheresis may be a more effective alternative to HP, although this remains to be investigated. 22,23 ENDNOTES ...
Objective
To describe the efficacy of in‐series hemoperfusion and hemodialysis in 2 dogs with carprofen overdose.
Case Summary
This report describes the treatment of 2 dogs following accidental carprofen overdoses who underwent a single in‐series hemoperfusion and hemodialysis session. Serial serum carprofen concentrations were measured before, during, and after the session. The first patient's session lasted 5 hours, with the largest decrease in serum carprofen concentrations occurring during the first hour of treatment. The carprofen clearance during the following 4 hours of treatment decreased substantially compared to the first hour and was not different from the patient's intrinsic clearance of carprofen after the session was completed. Based on the findings from the first case, the second patient was treated with a 1 hour single hemoperfusion and hemodialysis session. Our results support the hypothesis that carprofen is not effectively removed by conventional hemodialysis and the efficacy of hemoperfusion is short lived due to rapid saturation of the charcoal filter. Once filter saturation occurs, the extracorporeal session is no longer efficacious. Using in‐series hemoperfusion and hemodialysis is of benefit to correct the side effects seen with hemoperfusion alone, and hourly charcoal filter replacement may extend the efficacy of treatment in removing carprofen.
New or Unique Information Provided
This is the first published report of in‐series hemoperfusion and hemodialysis being used to treat carprofen overdose in a dog. In these 2 cases, the intrinsic clearances of the patients were shown to be equivalent to that of standard hemodialysis alone, indicating that hemodialysis does not produce any advantage in carprofen clearance. In this limited report, we suggest that the efficacy of hemoperfusion in removing carprofen is short‐lived, and extending the treatment beyond the first hour does not produce any therapeutic benefit. In order to extend the efficacy of hemoperfusion, hourly replacement of the charcoal filter should be considered.
... One technical complication because of low blood flow rates in a small-sized dog caused early discontinuation of the treatment, but all other treatments could be performed to satisfaction and reached >90% of the plasma exchange goal. The following complications were observed: vomiting (7 treatments), hemorrhagic diarrhea (1), sneezing (2), urticaria (1), laryngeal edema (1), chemosis (1), system clotting (2), and technical problem because of auto-test difficulties related to insufficiently low blood flow rates (5). Two dogs developed progressive dyspnea after completion of their treatments as a worsening of their preexisting leptospirosisassociated pulmonary hemorrhages and were therefore euthanized. ...
Background
Therapeutic plasma exchange (TPE) is used increasingly in small animals to remove circulating large molecular products such as antibodies, pathogenic proteins, and protein‐bound toxins. Specific, efficient, and safe protocols need to be developed.
Hypothesis/Objectives
To describe the technique of membrane‐based TPE, the resulting physiological and metabolic changes, and to define an adequate regional citrate anticoagulation protocol.
Animals
Thirty‐four dogs treated with TPE (2011‐2017).
Methods
Retrospective review of all TPE treatments performed at the Vetsuisse Faculty, University of Bern, identified through a search of the institutional database for extracorporeal treatments.
Results
Sixty‐four treatments were performed, resulting in 1.0 plasma volume exchange (range, 0.4‐1.1). Replacement fluids included fresh frozen plasma (12%‐100% volume), colloids (0%‐52%), human albumin (0%‐41%), and saline (0%‐70%). Anticoagulation was performed with regional citrate (n = 24), systemic heparinization (n = 2), or combined (n = 38). Main relevant laboratory changes included a 24.7% decrease in total proteins (interquartile range, 16.7‐31.4; P < .001), 53% in fibrinogen (−30 to 63; P = .009), 36% in bilirubin (13‐43, P = .02), 9.0% in urea (0.7‐15.7; P < .001), and 4.5% in creatinine (−6.6 to 10.6; P = .006). Citrate accumulation was evidenced in all dogs, more pronounced in those with renal but not with hepatic impairment. Maximal tolerable citrate rates were estimated as 5.5 and 9.0 μmol/kg/min for treatments in dogs with and without renal impairment, respectively. Complications were observed in 22 treatments (34%) and were fatal in 2 dogs.
Conclusions and Clinical Importance
Therapeutic plasma exchange causes metabolic and biochemical alterations. Understanding these effects makes possible to anticipate most complications and to improve safety of the procedure.
Objective
To report the use of manual therapeutic plasma exchange (TPE) in a dog with severe carprofen toxicity.
Summary
A 12‐year‐old neutered female Pembroke Welsh Corgi weighing 20 kg was evaluated after ingesting 223 mg/kg of carprofen. Emesis was attempted with apomorphine at the primary care veterinarian but was unsuccessful, and a dose of activated charcoal with sorbitol was administered. On presentation to the referral center, approximately 8 hours after ingestion, the dog's physical examination revealed mild abdominal discomfort but was otherwise unremarkable. Treatment consisted of a combination of supportive care including activated charcoal with sorbitol, cholestyramine, IV lipid emulsion, and manual TPE. Blood samples were collected prior to the initiation of manual TPE and at the completion of 12 exchange cycles. Carprofen levels were determined by high‐pressure liquid chromatography. A 57% decrease in carprofen levels was achieved with the combination of activated charcoal, cholestyramine, IV lipid emulsion, and manual TPE. The dog did not develop organ dysfunction secondary to toxicity and was discharged 4 days after ingestion.
New or Unique Information Provided
This report describes the successful decrease of plasma carprofen in a dog with the combination of decontamination techniques and manual TPE. While TPE has been previously reported as a successful therapeutic in dogs with nonsteroidal anti‐inflammatory toxicity, including carprofen, equipment and expertise of this platform is not readily available. Manual TPE is technically simple and can be performed in any hospital with a large blood centrifuge.
Background
The gastrointestinal and hepatic systems are the first to encounter many potentially toxic substances. Recognition, stabilisation and treatment of the consequences of intoxication are key to successful management.
Aim of the article
This is the final article in a series of four. It focuses on toxicants that affect the gastrointestinal or hepatobiliary systems, outlining the aetiology of the clinical signs observed, along with diagnostic assessment and treatment considerations.
Background
To compare the utility of a targeted smartphone application (TSPA) with a non-programmable calculator (NPC) when calculating fluid drip rates (FDR) and constant rate infusions (CRIs).
Methods
In a prospective randomised clinical study, 48 fourth-year veterinary students entered one of four parallel groups involving two mock scenarios: fentanyl calculation using an NPC followed by lidocaine calculation using a TSPA, fentanyl (TSPA) followed by lidocaine (NPC), lidocaine (NPC) followed by fentanyl (TSPA) or lidocaine (TSPA) followed by fentanyl (NPC). Students calculated volume of drug added to maintenance fluids and drops/second that correctly administered the drug dose and FDR. Time to completion was assessed using an analysis of variance. A Fisher’s exact test assessed the effect of study period, scenario and device in the proportion of correct/incorrect answers.
Results
Participants took longer to complete the scenarios in period 1 and 2 with the NPC (380.7±195.6 seconds and 488±154.8 seconds, respectively) than the TSPA (247.5±88.8 seconds and 224±94.2 seconds, respectively) (P<0.0031 and P<0.0001). Participants were more likely to complete the scenarios incorrectly with the NPC (n=32) when compared with the TSPA (n=7) (P<0.0001).
Conclusions
TSPAs are more efficient and accurate when calculating CRIs and FDR compared with conventional methods. Medical mathematics must be emphasised during the veterinary curriculum.
Objective
To describe the use of manual therapeutic plasma exchange (TPE) to manage hepatic encephalopathy (HE) in a dog.
Case summary
A 9‐year‐old neutered female Dachshund presented for HE secondary to a previously diagnosed portosystemic shunt. The hyperammonemia and severe clinical signs of HE persisted despite extensive medical management. Therapeutic plasma exchange was performed for stabilization prior to surgical shunt ligation. A total of 1 plasma volume was processed during a single manual TPE session. The ammonia immediately prior to TPE was 235 μmol/L (reference interval, 10‐30 μmol/L) and decreased to 117 μmol/L by the end of the session. The dog showed significant improvement in clinical signs shortly after the session and remained stable thereafter. Shunt ligation was performed 5 days later with no complications observed with TPE or postoperatively. The dog was discharged 3 days after surgery with no neurological signs and was doing well 100 days after surgery.
New or unique information provided
To the authors’ knowledge, this is the first published report of manual TPE to manage HE in veterinary medicine. Therapeutic plasma exchange should be further investigated as a possible strategy to manage clinical signs of HE in patients that are refractory to medical management. Achieving this with manual TPE may be considered in patients that are too small for conventional TPE due to extracorporeal volume or in situations where conventional TPE is not available.
A 3 yr old spayed female mixed-breed dog weighing 19.4 kg was evaluated for ingestion of 1,856 mg/kg (180 tablets) of ibuprofen, a human formulated nonsteroidal anti-inflammatory drug (NSAID). At the time of presentation, the patient was alert and hypersalivating, but her mental status rapidly declined to obtunded, stuporous, and then comatose within 30 min of presentation. Initial treatment included supportive therapy with prostaglandin analogs and antiemetics. An IV lipid emulsion (ILE) was administered as a bolus, followed by a constant rate infusion. Clinical signs began to improve approximately 3 hr after completion of the lipid infusion. The patient required supportive care for 3 days before discharge. This case report demonstrates the use of ILE for treatment of ibuprofen toxicosis in a dog. ILE infusion may be a therapeutic option for patients with toxicosis due to lipid-soluble drugs.
The potential for topical delivery of meloxicam was investigated by examining its pharmacokinetic profiles in plasma and synovial fluid following oral and transdermal administration in Beagle dogs.
The experiment was a two-period, crossover design using 6 Beagle dogs. Meloxicam tablets were administered orally at a dose of 0.31 mg/kg, and meloxicam gel was administered transdermally at a dose of 1.25 mg/kg. Drug concentrations in plasma and synovial fluid were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pharmacokinetic parameters were calculated using the Topfit 2.0 program.
The pharmacokinetic results showed that AUC(0-t) (23.9+/-8.26 microg.h.mL(-1)) in plasma after oral administration was significantly higher than after transdermal delivery (1.00+/-0.43 microg.h.mL(-1)). In contrast, the ratio of the average concentration in synovial fluid to that in plasma following transdermal administration was higher than that for an oral delivery. The synovial fluid concentration in the treated leg was much higher than that in the untreated leg, whereas the synovial fluid concentration in the untreated leg was similar to the plasma concentration.
The high concentration ratio of synovial fluid to plasma indicates direct penetration of meloxicam following topical administration to the target tissue. This finding is further supported by the differences observed in meloxicam concentrations in synovial fluid in the treated and untreated joints at the same time point. Our results suggest that transdermal delivery of meloxicam is a promising method for decreasing its adverse systemic effects.Acta Pharmacologica Sinica (2009) 30: 1060-1064; doi: 10.1038/aps.2009.73; published online 8 June 2009.
Volumes of distribution are proportionality constants between total amount of drug in the body and plasma concentrations. As snapshot plasma drug concentrations may be measured in different conditions (at equilibrium, under pseudo-equilibrium condition,...), several volumes of distribution have been defined. The two most relevant are the volume of distribution at equilibrium (V(ss)), and the volume of distribution during pseudo-equilibrium (V(area)). Volumes of distribution are used to compute a loading dose (V(ss)) or the residual amount of drug in the body knowing plasma concentrations (V(area)). Volume of distribution may be interpreted in terms of drug distribution having recourse to physiological models involving drug binding to plasma and tissues. Volumes of distribution should be determined early in drug development programmes and those having a large volume of distribution may be selected to obtain a long terminal half-life even for drugs having a relatively high clearance.
Plasma exchange (PE) is a technique of extracorporeal blood purification which removes large molecular weight substances from plasma. The Department of Dialysis, Zagreb University Hospital Center's database, which includes data on 509 patients, or 4857 PE treatments, was retrospectively analyzed to test the safety of PE. A total of 231 adverse reactions were recorded (4.75% of treatments). The most common complications were paresthesias (2.7%), hematoma at the puncture site (2.4%), clotting (1.7%), mild to moderate allergic reactions (urticaria; 1.6%) and bleeding (0.06%). True anaphylactoid reactions were recorded in five procedures. The incidence of severe, potentially life-threatening adverse reactions was 0.12%. The prophylactic use of calcium and potassium was responsible for a low incidence of electrolyte disturbances. There was no lethal outcome associated with PE. When carried out by experienced staff, PE is a relatively safe procedure. The use of fresh frozen plasma is associated with a higher rate of adverse reactions.
NSAIDs are the most widely used analgesics in veterinary medicine, and all have some toxic potential. The most common adverse class effects are gastrointestinal, renal, hepatic, and coagulation disorders. When treating chronic pain associated with osteoarthritis, the effectiveness of NSAIDs can be enhanced by physical therapy, use of chondroprotective agents, certain adjunctive drugs, and diet and exercise to control weight. To treat acute perioperative pain, NSAIDs are more effective when used preemptively, in the context of balanced (multimodal) analgesia, and in well-hydrated patients with normal blood pressure and renal function. Screening and monitoring to identify high-risk candidates for NSAID treatment should include a physical examination and patient history, identification of preexisting diseases or conditions, obtaining baseline and periodic hematologic and clinical chemistry values, and ensuring that other NSAIDs or contraindicated drugs are not used concurrently. When switching a patient from one NSAID to another (when no side effects have been seen), a washout period of 5 to 7 days minimizes chances for adverse drug interactions. Informing clients of the potential adverse effects of NSAID therapy and signs of NSAID toxicity greatly increases the likelihood of safe use of this class of drugs.
Plasma removal (plasmapheresis) directly removes pathogenic autoantibodies and other plasma factors (eg cytokines) to provide temporary therapeutic benefit Relapse is likely without concurrent immunosuppression and/or other appropriate treatment of the underlying condition (preventing autoantibody production) Plasmapheresis is a limited resource, largely limited to regional centres; it requires staff experienced in use of specialist apheresis machines Alternative treatments should be used first (eg Guillain-Barré syndrome for which intravenous immunoglobulin therapy is equally effective) Commoner side effects relate to central-line insertion, loss of plasma clotting factors and hypocalcaemia caused by citrate anticoagulation.
To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs.
36 adult dogs.
Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment.
For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen.
Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.
To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum.
18 horses.
Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed.
Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flunixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cyclooxygenase-independent effects.
Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.
Contrary to the literature about drug removal during hemodialysis, data regarding drug removal during plasmapheresis are sparse. Over the last 40 years, approximately 70 publications-mostly case reports of overdoses-have described the effects of plasmapheresis on pharmaceutical agents. Important issues are drug extraction during plasma exchange with chemotherapy, as well as drug classes such as antiinfectives, anticoagulants, antiepileptics, cardiovascular agents, and immunosuppressants. Other considerations are the merits and pitfalls of the different methods used in published reports and recommendations for future pharmacokinetic studies in this field.
Plasma exchange is a therapeutic procedure used to treat a variety of diseases through the bulk removal of plasma. To apply this treatment to patients appropriately, it is essential to understand the methods to remove plasma, its effects on normal plasma constituents, the role of replacement fluids in the treatment, and the risks associated with the procedure. To facilitate the appropriate evidence-based use of plasma exchange and to encourage research, the American Society for Apheresis has published guidelines providing practical guidance and information to those responsible for ordering or providing this treatment.
Comprehensive Clinical Nephrology provides you with all the tools you need to manage all forms of kidney disease. Drs. Jürgen Floege, Richard J. Johnson, John Feehally and a team of international experts have updated this fourth edition to include hot topics such as treatment of hypertensive emergencies, herbal and over-the-counter medicines and the kidney, neurologic complications of the kidney, and more. In print and online at www.expertconsult.com, this essential resource gives you quick access to today's best knowledge on every clinical condition in nephrology. Make efficient, informed decisions with just the right amount of basic science and practical clinical guidance for every disorder.Diagnose effectively and treat confidently thanks to more than 1100 illustrations, abundant algorithms, and tables that highlight key topics and detail pathogenesis for a full range of kidney conditions and clinical management.Access the fully searchable text online at www.expertconsult.com, along with a downloadable image gallery.Get coverage of the latest developments in the field with 18 new chapters on the Management of the Diabetic Patient with Chronic Kidney Disease, Treatment of Hypertensive Emergencies, Principles of Drug Dosing and Prescribing of Chronic Kidney Disease, Herbal and Over-the-Counter Medicines and the Kidney, Neurologic Complications of the Kidney, and more.Tap into the experience and expertise of the world's leading authorities in the field of nephrology.Floege, Johnson, and Feehally give you the information you need to make quick and correct clinical decisions.
NSAIDs are a group of drugs used widely in both animals and humans. The main applications of NSAIDs are for the treatment of pain, inflammation and pyrexia. The primary mechanism of action of NSAIDs is inhibition of cyclo-oxygenase. This results in a reduction of the synthesis of prostaglandins, which are mediators of inflammation. This inhibition also causes a number of side effects, particularly on the gastro-intestinal tract and the kidneys. It is possible to reduce the risk of side effects by knowing the predisposing factors and administering prophylactic medication. This article reviews the side effects of both human and animal approved NSAIDs in dogs and cats. The mechanisms which are responsible for the adverse effects are discussed as well as risk factors, prevention and treatment, and recent discoveries for the development of future NSAIDs.
The clinical applications of plasmapheresis are rapidly increasing in number and scope. This trend is also observed in the application of plasmapheresis as a method of detoxification in clinical toxicology. Because of a lack of large controlled series, the rationale for using plasmapheresis must be confirmed in each type of intoxication by evidence of effective clearance, as well as by high plasma protein binding and a low volume of distribution of the toxic substance. Plasmapheresis is used mostly to treat phalloid mushroom intoxications. In this potentially fatal intoxication, for which there is no antidote, plasmapheresis is at least as effective as haemoperfusion in reducing mortality from as high as 30–50% with conventional therapy to <20%. In our series of 28 patients treated with plasmapheresis, mortality was 17.8%. In our experience, plasmapheresis is also very effective in the treatment of lifethreatening intoxications with tricyclic (amitriptyline) and 4-cyclic (maprotyline) antidepressants. We confirmed a 63% reduction in the plasma level of amitriptyline in one patient after single plasmapheresis. Other drugs such as L-thyroxine, verapamil, diltiazem and carbamazepime are also removed effectively by plasmapheresis, as are theophylline and heavy metals (mercury and vanadate). Phosphoroorganic substances are not removed effectively. We measured the plasma concentrations of dimethoate in two patients with this intoxication and did not find clinically significant clearance with plasmapheresis.
To (1) review the development and medical applications of hydroxyethyl starch (HES) solutions with particular emphasis on its physiochemical properties; (2) critically appraise the available evidence in human and veterinary medicine, and (3) evaluate the potential risks and benefits associated with their use in critically ill small animals.
Human and veterinary original research articles, scientific reviews, and textbook sources from 1950 to the present.
HES solutions have been used extensively in people for over 30 years and ever since its introduction there has been a great deal of debate over its safety and efficacy. Recently, results of seminal trials and meta-analyses showing increased risks related to kidney dysfunction and mortality in septic and critically ill patients, have led to the restriction of HES use in these patient populations by European regulatory authorities. Although the initial ban on the use of HES in Europe has been eased, proof regarding the benefits and safety profile of HES in trauma and surgical patient populations has been requested by these same European regulatory authorities.
The veterinary literature is limited mostly to experimental studies and clinical investigations with small populations of patients with short-term end points and there is insufficient evidence to generate recommendations.
Currently, there are no consensus recommendations regarding the use of HES in veterinary medicine. Veterinarians and institutions affected by the HES restrictions have had to critically reassess the risks and benefits related to HES usage based on the available information and sometimes adapt their procedures and policies based on their reassessment. Meanwhile, large, prospective, randomized veterinary studies evaluating HES use are needed to achieve relevant levels of evidence to enable formulation of specific veterinary guidelines.
© Veterinary Emergency and Critical Care Society 2015.
Objectives – To (1) review the development and medical applications of hydroxyethyl starch (HES) solutions with particular emphasis on its physiochemical properties; (2) critically appraise the available evidence in human and veterinary medicine, and (3) evaluate the potential risks and benefits associated with their use in critically ill small animals. Data Sources – Human and veterinary original research articles, scientific reviews, and textbook sources from 1950 to the present. Human Data Synthesis – HES solutions have been used extensively in people for over 30 years and ever since its introduction there has been a great deal of debate over its safety and efficacy. Recently, results of seminal trials and meta-analyses showing increased risks related to kidney dysfunction and mortality in septic and critically ill patients, have led to the restriction of HES use in these patient populations by European regulatory authorities. Although the initial ban on the use of HES in Europe has been eased, proof regarding the benefits and safety profile of HES in trauma and surgical patient populations has been requested by these same European regulatory authorities. Veterinary Data Synthesis – The veterinary literature is limited mostly to experimental studies and clinical investigations with small populations of patients with short-term end points and there is insufficient evidence to generate recommendations. Conclusions – Currently, there are no consensus recommendations regarding the use of HES in veterinary medicine. Veterinarians and institutions affected by the HES restrictions have had to critically reassess the risks and benefits related to HES usage based on the available information and sometimes adapt their procedures and policies based on their reassessment. Meanwhile, large, prospective, randomized veterinary studies evaluating HES use are needed to achieve relevant levels of evidence to enable formulation of specific veterinary guidelines.
Objective
To review and summarize the pharmacokinetics and pharmacodynamics of hydroxyethyl starch (HES), as well as reported risks and benefits of HES infusion, and to provide administration and monitoring recommendations for HES use in dogs and cats.Data SourcesVeterinary and human peer-reviewed medical literature, including scientific reviews, clinical and laboratory research articles, and authors’ clinical experience.SummaryHES solutions are the most frequently used synthetic colloid plasma volume expanders in human and veterinary medicine. The majority of research in human medicine has focused on the adverse effects of HES infusion, with emphasis on acute kidney injury and coagulation derangements. The studies often differ in or fail to report factors, such as the type, amount, interval, and concentration of HES administered; the patient population studied; or concurrent fluids administered. Currently, there is no definitive clinical evidence that the reported adverse effects of HES use in human medicine occur in veterinary species. There is little information available on HES administration techniques or simultaneous administration of additional fluids in human and veterinary medicine. The rationale for HES use in small animals has been largely extrapolated from human medical studies and guidelines. A controlled approach to intravenous fluid resuscitation using crystalloid and HES volumes titrated to reach desired resuscitation end point parameters is outlined for small animal practitioners.Conclusion
The extrapolation of data from human studies directly to small animals should be done with the knowledge that there may be species variations and different pharmacokinetics with different HES solutions. Veterinary reports indicate that bolus and continuous rate infusions of 6% hetastarch solutions at moderate doses are well tolerated in feline and canine subjects. Further research in domesticated species is necessary to better define and expand the knowledge regarding use of HES solutions in small animal medicine.
A retrospective study was conducted on the exposure of dogs and cats to drugs, reported to the Poison Control Centre of Milan (Centro Antiveleni di Milano (CAV)) between January 2006 and December 2012. Calls related to drugs for human use and veterinary drugs accounted for 23.7 per cent of total inquiries (1415) received by CAV and mostly involved dogs (70 per cent of enquiries). Exposure to drugs for human use accounted for 79 per cent of cases involving dogs, whereas veterinary drugs were the main culprit (77 per cent) in the case of cats. The most common class of drugs for human use proved to be CNS drugs (26.8 per cent), followed by NSAIDs (19.6 per cent) and cardiovascular and endocrine drugs (12.9 per cent each). The majority of calls (95.2 per cent) related to veterinary drugs involved dogs and cats exposed to parasiticides. The outcome was reported in only 58.2 per cent of cases, and fatal poisoning accounted for 8.7 per cent of these cases. Epidemiological data from this Italian survey provide useful information on animal exposure to drugs. The knowledge of agents involved in poisoning episodes can help veterinarians make the correct diagnosis and institute preventive measures to possibly reduce animal exposure to drugs.
The aim of this systematic review was to identify, assess, and critically evaluate the quality of evidence of nonsteroidal anti-inflammatory drug (NSAID)-induced adverse effects in dogs. Original prospective studies published in peer-reviewed journals in English (1990-2012) that reported data on the safety of NSAIDs administration in dogs were searched. For each study, design type (I, II, III, or IV) and assessment of quality (+, Ø, -) were rated. For each drug, quantity and consistency rating (***, **, *) and strength of evidence (high, moderate, low, or extremely low) were identified and evaluated. The strength of evidence was defined in terms of how applicable and relevant the conclusions were to the target population. Sixty-four studies met the inclusion criteria. Thirty-five (55%) research studies and 29 (45%) clinical trials were identified. A high strength of evidence existed for carprofen, firocoxib, and meloxicam; moderate for deracoxib, ketoprofen, and robenacoxib; and low for etodolac. Quality and consistency rating were as follows: carprofen (***/***), deracoxib (**/***), etodolac (*/unable to rate), firocoxib (***/**), ketoprofen (**/***), meloxicam (***/***), and robenacoxib (**/**), respectively. Adverse effects were detected in 35 studies (55%) and commonly included vomiting, diarrhea, and anorexia. Three studies (5%) reported a power analysis related to adverse effects of ≥80%. In randomized, placebo-controlled, blinded studies (n = 25, 39%), the incidence of adverse effects was not statistically different between treated and control dogs. Finally, most studies were not appropriately designed to determine the safety of NSAIDs, and involved a healthy nongeriatric population of research dogs.
Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique designed for the removal of large molecular weight substances. Examples of these substances include pathogenic autoantibodies, immune complexes, cryoglobulins, myeloma light chains, endotoxin and cholesterol containing lipoproteins. The basic premise of the treatment is that removal of these substances will allow for the reversal of the pathologic processes related to their presence. This review will cover the techniques for performing TPE, the kinetics of the removal of large molecules from the plasma and the benefits and risks of the different types of replacement fluids. J. Clin. Apheresis 28:3-10, 2013. © 2013 Wiley Periodicals, Inc.
Plasma exchange is a therapeutic procedure used to treat a variety of diseases through the bulk removal of plasma. To apply this treatment to patients appropriately, it is essential to understand the methods to remove plasma, its effects on normal plasma constituents, the role of replacement fluids in the treatment, and the risks associated with the procedure. To facilitate the appropriate evidence-based use of plasma exchange and to encourage research, the American Society for Apheresis has published guidelines providing practical guidance and information to those responsible for ordering or providing this treatment.
Objective – To investigate the clinical application and potential utility of plasmapheresis in canine immune-mediated hemolytic anemia.
Case Summary – A 7-year-old spayed female Maltese diagnosed with immune-mediated hemolytic anemia was initially treated with prednisone, cyclosporine, and received multiple transfusions of packed RBC. Because of the progression of clinical signs despite traditional medical therapy, plasmapheresis was initiated. Plasma immunoglobulin G and immunoglobulin M levels were measured before, during, and after treatment to help determine if there had been a significant decrease in immunoglobulin levels with plasmapheresis. Plasmapheresis was successfully performed over a 2.5-hour period in this dog with minimal complications. Hypocalcemia was identified as a known complication of circuit anticoagulation, and was corrected through calcium supplementation. Post-plasmapheresis there was a decrease in immunoglobulin G and immunoglobulin M levels, and the patient showed clinical improvement. Following discharge the dog had no known complications of therapy, and had complete resolution of the anemia.
New or Unique Information Provided – Plasmapheresis was performed successfully with minimal complications. Because transfusion requirements appeared to be reduced, and the procedure was well tolerated, there may be a place for this modality in severe cases to act as a bridge until medical therapy takes full effect. Because of the cost of performing this therapy, and the potential requirement for multiple treatments, it should be reserved for selected patients.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of heterogeneous compounds extensively used in both human and veterinary medicine for their antipyretic, anti-inflammation, and analgesic properties. NSAIDs consist of a wide range of pharmacologically active agents with different chemical structures, with similar therapeutic and adverse effects. The ASPCA Animal Poison Control Center received 22,206 NSAID incidents in dogs and cats (3% of total cases; dogs [15,823] and cats [1244]) during 2005 to 2010. This is roughly equivalent to 4% NSAID incidents reported in humans. The most common NSAID involved was ibuprofen, followed by aspirin, naproxen, deracoxib, meloxicam, diclofenac, piroxicam, indomethacin, nabumetone, and etodolac. This article provides a brief overview of classification, mechanism of action, pharmacologic and toxicologic properties, and treatment information involving frequently encountered human and veterinary NSAIDs in dogs and cats.
Poisonings, intoxications, and drug overdoses are common occurrences and rapid lowering of the toxin level is a cornerstone of all effective therapies. Therapeutic plasma exchange (TPE) has several unique characteristics that allow it to be a potentially effective therapy in rapidly achieving this goal. Specifically, TPE allows for the removal of large molecular weight, protein-bound molecules that have a small volume of distribution. Due to the nature of poisonings, intoxications, and drug overdoses, no randomized controlled trials studying the efficacy of TPE in these situations exist. Thus, careful interpretation and analysis of case reports and series are required to assess the potential efficacy of this therapy. Recent data suggest that TPE may also be effective in the therapy of patients receiving biologic treatments who develop life-threatening complications due to therapy.
Therapeutic plasma exchange (TPE) is an extracorporeal process commonly used in clinical medicine for the treatment of a variety of neurological, renal, hematological, dermatological, and other diseases. Inherent to the procedure, patients' plasma removal may lead to the extraction of drugs they are concurrently receiving. This review discusses the published literature assessing TPE's influence on different drug classes' disposition and, when applicable, sets forth management recommendations in cases where the drugs are used at the usual doses and in cases of drug overdose.
Therapeutic plasma exchange (TPE) has been firstly performed with centrifugation devices used in blood banking procedures. Nowadays, TPE is increasingly performed in intensive care units using hemodiafiltration generators that ensure better efficiency and simplicity. However, prescription for the different medical pathologies depends on weak evidence-based recommendations, and is often guided by the clinician's own experience. In this review, we briefly recall the rationale of TPE prescription before discussing the evidence level of common indications of TPE in nephrology. Currently, strong evidence-based data for the benefit of TPE is clearly demonstrated in renal diseases such as hemolytic uremic syndrome, anti-glomerular basement membrane vasculitis, and recurrent glomerulonephritis after kidney transplantation and management of humoral renal allograft rejection in high-risk recipients. However, the other indications of TPE, such as renal vasculitis associated with anti-neutrophil cytoplasmic antibodies, mixed cryoglobulinemia, periarteritis nodosa, and acute renal failure in myeloma are still controversial. Finally, TPE have been found to be clearly inefficient in lupus nephritis, except for patients with associated thrombotic mic-roangiopathy or catastrophic antiphospholipid antibodies syndrome. More randomized clinical trials are required to precisely place TPE in the management of renal diseases. Meanwhile, the decision to use this burdensome and costly therapy should be individualized according to its proven benefits and potential complications.
Ingvast-Larsson, C., Högberg, M., Mengistu, U., Olsén, L., Bondesson, U., Olsson, K. Pharmacokinetics of meloxicam in adult goats and its analgesic effect in disbudded kids. J. vet. Pharmacol. Therap.34, 64–69.
The pharmacokinetics and analgesic effect of the nonsteroidal anti-inflammatory drug meloxicam (0.5 mg/kg) in goats were investigated. In a randomized, cross-over design the pharmacokinetic parameters were investigated in adult goats (n = 8) after single intravenous and oral administration. The analgesic effect was evaluated in kids using a randomized, placebo controlled and blinded protocol. Kids received meloxicam (n = 6) once daily and their siblings (n = 5) got isotonic NaCl intramuscularly while still anaesthetized after cautery disbudding and injections were repeated on three consecutive days. In the adult goats after intravenous administration the terminal half-life was 10.9 ± 1.7 h, steady-state volume of distribution was 0.245 ± 0.06 L/kg, and total body clearance was 17.9 ± 4.3 mL/h/kg. After oral administration bioavailability was 79 ± 19%, Cmax was 736 ± 184 ng/mL, Tmax was 15 ±5 h, although the terminal half-life was similar to the intravenous value, 11.8 ± 1.7 h. Signs of pain using a visual analogue scale were smaller in kids treated with meloxicam compared with kids treated with placebo on the first day after disbudding, but subsequently no difference in pain was noticeable. Plasma cortisol and glucose concentrations did not differ between the two groups.
In vitro whole blood canine assays were used to quantify the inhibitory actions of the novel non-steroidal anti-inflammatory drug (NSAID) robenacoxib on the cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, in comparison with other drugs of the NSAID class. COX-1 activity was determined by measuring serum thromboxane (Tx)B(2) synthesis in blood samples allowed to clot at 37 degrees C for 1h. COX-2 activity was determined by measuring prostaglandin (PG)E(2) synthesis in blood samples incubated at 37 degrees C for 24h in the presence of lipopolysaccharide. The rank order of selectivity for inhibition of COX-2 versus COX-1 (IC(50) COX-1:IC(50) COX-2) for veterinary drugs was highest with robenacoxib (128.8) compared to deracoxib (48.5), nimesulide (29.2), S+ carprofen (17.6), meloxicam (7.3), etodolac (6.6), R- carprofen (5.8) and ketoprofen (0.88). Selectivity expressed as the clinically relevant ratio IC(20) COX-1:IC(80) COX-2 was highest for robenacoxib (19.8) compared to deracoxib (2.3), S+ carprofen (2.5), R- carprofen (2.1), nimesulide (1.8), etodolac (0.76), meloxicam (0.46) and ketoprofen (0.21). An in vivo pharmacokinetic ex vivo pharmacodynamic study in the dog established dosage and concentration-effect relationships for single oral doses of robenacoxib over the dosage range 0.5-8.0mg/kg. Values of C(max) and AUC were linearly related to dosage over the tested range. Robenacoxib did not inhibit serum TxB(2) synthesis (COX-1) ex vivo at dosages of 0.5-4.0mg/kg and produced only transient inhibition (at the 1h and 2h sampling times) at the 8mg/kg dosage. All dosages of robenacoxib (0.5-8mg/kg) produced marked, significant and dose related inhibition of PGE(2) synthesis (COX-2) ex vivo. The data demonstrate that in the dog robenacoxib is a highly selective inhibitor of the COX-2 isoform of COX, and significantly inhibits COX-2 and spares COX-1 in vivo when administered orally over the dosage range 0.5-4.0mg/kg.
Plasma exchange (PE) is used for blood purification to modulate proteins involved in pathological processes. As the number of patients receiving PE treatment and the heterogeneity of the underlying diseases is steadily increasing, we evaluated the most frequent complications and analyzed causes leading to adverse reactions. 883 PE procedures in 113 patients between the years 2000 to 2006 were retrospectively analyzed with respect to complications. Additionally, underlying diseases and settings of PE procedure were analyzed to identify high-risk patients and respective PE settings. A total of 226 adverse reactions were recorded (25.6% of all PE procedures). Most complications were mild (n = 121, 13.7%) or moderate (n = 98, 11.0%). In seven cases (n = 7, 0.7%), severe, life-threatening adverse events were induced by PE either due to severe allergic reactions (n = 4, 0.5%) or to sepsis (n = 3, 0.3%). Patients with neurologic diseases had a significantly higher risk to develop complications compared to those with internal diseases (P = 0.013). This was due to a higher rate of PE associated adverse events (in particular hypotension) and complications associated with vascular access. Among patients from internal medicine those with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) had the highest risk to develop complications. Patients with neurological diseases compared to those with medical conditions and patients with HUS/TTP compared to those with other diseases had a higher risk to develop complications. However, severe adverse events are rare. Thus, PE seems to be a safe and recommendable procedure.
There are several choices of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating dogs that have osteoarthritis. However, fewer drugs are available for cats. Like people, there may be greater differences among individuals in their response than there are differences among the drugs. In past practice, veterinarians often selected aspirin or phenylbutazone as an initial drug, and then progressed to off-label human drugs or other agents as an alternative. Now we have the advantage of several approved NSAIDs for which there are excellent published studies and US Food and Drug Administration or foreign approval to guide clinical use and safe dosages.
A 7-year-old sexually intact male Labrador Retriever with regurgitation and generalized muscular weakness resulting from acquired myasthenia gravis received 2 plasmapheresis treatments in combination with corticosteroid treatment. Plasmapheresis was performed in an attempt to rapidly lower serum acetylcholine receptor binding antibody (AChR Ab) concentration. Seven days after the second plasmapheresis treatment, the dog's muscular strength was normal, which coincided with a 70% decrease in serum AChR Ab concentration. Because the dog also received corticosteroids, it is impossible to determine how much of the clinical improvement resulted from plasmapheresis.
Severe, acute, autoimmune hemolytic anemia in 2 dogs was treated, using prednisone, cyclophosphamide, plasmapheresis, and blood transfusion. In 1 case, splenectomy was performed successfully after plasmapheresis and blood transfusion. Antibody removal by means of plasmapheresis effected short-term stabilization to severe hemolysis in both dogs, but was suspected to have contributed to the death of 1 dog.
Although the elimination of specific toxins by the removal of all plasma constituents is a crude approach, further refinements of the technique should permit safer and more selective detoxification in the future. Currently the mainstay of treatment of intoxicated patients remains careful, aggressive, supportive care. Plasmapheresis should be considered as yet an unproven, hazardous form of therapy for the treatment of intoxication. Its main role should be confined to a research setting in which investigators attempt to develop more advanced and potentially useful apheresis techniques. Membrane plasmapheresis with subsequent on-line treatment of the plasma by sorbent may remove specific plasma solutes. The plasma may be perfused back to the patient without the need to use replacement fluids, thus avoiding many of the side effects of conventional exchange. Bile acids have been removed by circulating plasma over charcoal-coated glass beads, and several toxic substances were shown to be absorbed by perfusion over amberlite resin columns. Another productive area for future research includes the use of plasma exchange therapy for the treatment of acute endogenous intoxications. Recent examples include the treatment of severe preeclampsia, extensive rhabdomyolysis, and life-threatening bleeding in a hemophiliac with inhibitors to clotting factors. Although plasmapheresis in the management of intoxications is still an experimental technique, it may open the door to the treatment of previously intractable syndromes, both medical and toxicologic.
Monoclonal gammopathy associated with Ehrlichia canis infection was diagnosed in a German Shepherd Dog. The dog was treated by use of chemotherapy and tetracycline and by plasmapheresis. The dog tolerated plasmapheresis and long-term drug therapy well, and clinical signs resolved over a 90-day period. The monoclonal gammopathy resolved after treatment, but specific antibody to E canis indicated suppression followed by a rebound to the initial high titer.
Five dogs with signs referable to systemic immune-mediated disease, four with systemic lupus erythematosus, and one with probable lupus myopathy were treated with plasmapheresis in combination with low-dose immunosuppressive drug therapy. Previous treatment with conventional dosages of prednisone was not satisfactory and was associated with adverse side effects. Two dogs had short-term responses to combined therapy, and 3 dogs had sustained responses. Clinical remission was associated with normalization of serum complement levels and decreases in antinuclear antibody titers. Toxicosis potentially related to plasma component depletion was observed in 2 dogs. Acute clinical illness and disease states refractory to conventional immunosuppressive therapy should be considered indications for plasmapheresis.
Systemic lupus erythematosus was diagnosed in a 3-year-old, male German Shepherd Dog. Clinical signs included lethargy, partial anorexia, fever, joint swelling, and skin and oral ulceration. The diagnosis was confirmed on the basis of an antinuclear antibody titer of 1:640 and immunofluorescence for immunoglobulin G at the dermal-epidermal junction in skin biopsy specimens. Treatment with prednisone and cyclophosphamide failed to induce remission. Intensive plasmapheresis-immunoadsorption, using purified Staphylococcus protein A in combination with low-dose prednisone therapy, resulted in sustained remission.
Hyperviscosity syndrome associated with IgA monoclonal gammopathy was diagnosed in 3 dogs. Continuous plasmapheresis and alkylation therapy with melphalan and cyclophosphamide induced sustained remission in each dog. There was resolution of clinical signs associated with hyperviscosity syndrome and rapid establishment of normal serum protein concentrations.
The pharmacokinetic profile of the new nonsteroidal anti-inflammatory drug meloxicam was investigated in a number of animal species, including mice, rats, dogs, mini-pigs, and baboons, after administration of [14C]meloxicam. The plasma concentration-time profiles for meloxicam in rats and dogs were comparable to that in humans, whereas there were marked differences between humans and mice, mini-pigs, and baboons. The highest tissue concentrations of meloxicam in rats and mini-pigs were seen in the liver and kidneys. In contrast, low concentrations of meloxicam were found in the central nervous system, compared with those in plasma. The excretion balance in mini-pigs resembled that in humans, with almost equal concentrations being eliminated in the urine and the feces. As in humans, meloxicam circulated mainly in the form of the parent compound in the plasma of mice, rats, dogs, mini-pigs, and baboons. The main metabolites in rats, mini-pigs, and humans were a 5'-hydroxymethyl derivative (AF-UH 1 SE) and a 5'-carboxy metabolite (UH-AC 110 SE). The percentage of meloxicam binding to protein was higher in rats and humans (>99%) than in other species. The pharmacokinetic profile of meloxicam in rats most closely resembles that in humans; therefore, reliable clinical predictions can be made from studies in this rodent species.
Nonsteroidal anti-inflammatory analgesics (NSAIAs) are effective in controlling most acute and chronic pain conditions. In veterinary practice these analgesics may be superior to opioids in that the duration of action is much longer, with equal efficacy in many instances, making effective pain management possible for most veterinary patients. NSAIAs act synergistically in combination with other modalities of pain management, including all opioids, local anesthetics, and various sedatives. Because of their mechanism of action, however, there is a potential for perturbation of several homeostatic functions mediated by prostaglandins. Not all NSAIAs are equal in efficacy and safety, so careful patient and NSAIA selection with appropriate monitoring is advised. This article discusses the indications and contraindications for NSAIA use with a short description of the currently available NSAIAs approved for use in veterinary patients.
After more than a century of use, pharmacologists thought they had discovered the mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) when their inhibitory action on the production of prostaglandins was described. This action was located at the inhibition of the enzyme responsible for the conversion of arachidonic acid to prostaglandins, namely cyclo-oxygenase. More recently, it has been recognized that more than one isoform of the enzyme exists. The two forms of cyclo-oxygenase described are widely different in their location, activity, and role, especially because the COX-1 isoenzyme seems to be mainly a constitutive enzyme whereas the COX-2 isoenzyme is inducible. This separation of activity appears to be correlated with the separation of function of the various prostaglandins, whereas the constitutive form is associated with "physiologic" functions and the inducible form with inflammatory responses. Recent advances have included the development of drugs with a high specificity toward the inducible enzyme (COX-2) to focus on the anti-inflammatory actions, because many of the unwanted side effects of NSAIDs have been associated with inhibition of the constitutive isoform (COX-1). Other recent developments in studies of the NSAIDs have included potential therapeutic actions in other degenerative conditions.
Hypocalcemic toxicity accounts for the most common adverse effects of therapeutic plasma exchange. The symptoms can be related to a fall in plasma ionized calcium. Citrate-based anticoagulants, notably sodium citrate and ACD formula A, have been indicated as the major cause of hypocalcemic toxicity, but colloid replacement fluids containing human serum albumin are also at fault. Recognition of the signs and symptoms of hypocalcemic toxicity is important because several clinical measures are available to deal with them and to ensure patient comfort. A typical reactions, characterized by flushing and hypotension during plasma exchange, have been attributed to the effects of angiotensin converting enzyme inhibitors. Both exchange and adsorption apheresis procedures can result in atypical reactions in patients who have been taking this class of drugs within 48 to 72 hours of an apheresis procedure. These reactions are less common than hypocalcemic toxicity, but can be prevented by paying attention to detail.
The increasing use of nonsteroidal antiinflammatory drugs (NSAIDs) in small animals has resulted in the development of new and innovative additions to this class of drugs. Examples of NSAIDs now available for use in small animals include aspirin, etodolac, carprofen, ketoprofen, meloxicam, deracoxib, and tepoxalin. The purposes of this article are to review the pathophysiology of prostaglandin synthesis and inhibition, the mechanisms of action, pharmacokinetics, pharmacological effects, and potential adverse reactions of aspirin and the newly released NSAIDs.
The type and number of complications was prospectively examined in 1,727 successive TPE treatments in 174 patients over 66 months at a single center. Most treatments were prescribed for thrombotic thrombocytopenic purpura (TTP; 42%), recurrent focal segmental glomerulosclerosis (FSGS; 22%), or myasthenia gravis (MG; 13%). About 57% of treatments used albumin-saline as the replacement solution and 43% used fresh-frozen plasma (FFP), almost all for TTP. There were 889 complications; 614 treatments (36% of the total) involved a complication. Most complications were minor; there were no deaths. Three treatments (0.2%) were discontinued due to a complication, and 2 (0.1%) required transfer to a higher acuity hospital bed. The most common complications were fever (7.7% of treatments), urticaria (7.4%), and hypocalcemic symptoms (7.3%). 42% of treatments with FFP involved a complication, compared to 30% of treatments using albumin-saline (P < 0.0001). The most common complications with FFP were urticaria (17%) and pruritus (13%); these occurred more commonly than in patients receiving albumin-saline. The most common complications with albumin-saline replacement were hypocalcemic symptoms (8.2%) and mild hypotension (8.1%). Mild and severe hypotension was significantly (P < 0.0001) more common with albumin-saline replacement. TPE is associated with a number of minor complications. Complications occur more commonly with FFP replacement compared to albumin-saline replacement. Pruritus and urticaria occur more commonly with FFP, and hypotension occurs more commonly with albumin-saline.
American Society of Hematology Program (ASH) 54th Annual Meeting
- Winters JL
Small Animal Toxicology
- Talcott PA
- Gwanltney-Brant SM
Pharm profile: meloxicam
- Wallace JM
A Practical Guide to Therapeutic Plasma Exchange
- Kaplanaa
Complications of therapeutic plasma exchange: a prospective study of 1,727 procedures
- Shemin D
- Griggs D
- Greenan M