- Journal List
- Can Vet J
- v.56(6); 2015 Jun
- PMC4431157
A retrospective analysis of 25% human serum albumin supplementation in hypoalbuminemic dogs with septic peritonitis
Abstract
This study describes the influence of 25% human serum albumin (HSA) supplementation on serum albumin level, total protein (TP), colloid osmotic pressure (COP), hospital stay, and survival in dogs with septic peritonitis. Records of 39 dogs with septic peritonitis were evaluated. In the HSA group, initial and post-transfusion TP, albumin, COP, and HSA dose were recorded. In the non-supplemented group, repeated values of TP, albumin, and COP were recorded over their hospitalization. Eighteen dogs survived (53.8% mortality). Repeat albumin values were higher in survivors (mean 23.9 g/L) and elevated repeat albumin values were associated with HSA supplementation. Repeat albumin and TP were higher in the HSA supplemented group (mean 24 g/L and 51.9 g/L, respectively) and their COP increased by 5.8 mmHg. Length of hospitalization was not affected. Twenty-five percent HSA increases albumin, TP, and COP in canine patients with septic peritonitis. Higher postoperative albumin levels are associated with survival.
Résumé
Analyse rétrospective d’un supplément de 25 % d’albumine sérique humaine chez les chiens hypoalbuméniques souffrant d’une péritonite septique. Cette étude décrit l’influence d’un supplément de 25 % d’albunine sérique humaine (ASH) sur le niveau d’albumine sérique, de protéines totales (PT), sur la pression osmotique colloïdale (POC), la durée du séjour à l’hôpital et la survie des chiens souffrant de péritonite septique. Les dossiers de 39 chiens souffrant de péritonite septique ont été évalués. Dans le groupe ASH, la PT, l’albumine, le POC et l’ASH initiaux et post-transfusion ont été consignés. Dans le groupe sans supplément, des valeurs répétées de PT, d’albumine et de POC ont été notées pendant l’hospitalisation. Dix-huit chiens ont survécu (mortalité de 53,8 %). Les nouvelles valeurs d’albumine étaient supérieures chez les survivants (moyenne de 23,9 g/L) et les nouvelles valeurs d’albumine élevées étaient associées à un supplément d’ASH. Les nouvelles valeurs d’albumine et de PT étaient supérieures dans le groupe ayant reçu le supplément d’ASH (moyenne de 24 g/L et 51,9 g/L, respectivement) et leur POC a augmenté de 5,8 mmHg. La durée de l’hospitalisation n’était pas affectée. Le 25 % d’ASH augmente l’albumine, la PT et le POC chez les patients canins atteints de péritonite septique. Des niveaux d’albumine postopératoire supérieurs étaient associés à la survie.
(Traduit par Isabelle Vallières)
Introduction
Hypoalbuminemia is commonly associated with critical illness and can result in serious complications including multi-organ failure, poor wound healing, pulmonary edema, and coagulopathy (1). It prolongs hospital stay, increases complications while patients are hospitalized, and increases morbidity and mortality (1–5). In dogs, septic peritonitis is associated with a mortality rate ranging from 21% to 68% (6–11). Hypoalbuminemia is commonly encountered in these critically ill dogs and may be associated with an increased risk of death (1,9,12).
Intravenous infusion of albumin corrects hypoalbuminemia while contributing the advantages albumin has over synthetic colloids including carrying drugs and endogenous substances, mediating coagulation, and inhibiting oxidative damage (13,14). Sources of albumin in dogs include canine specific albumin, plasma, and human serum albumin (HSA). Species specific albumin supplementation in dogs following surgery for septic peritonitis increased albumin level and colloid osmotic pressure (COP) with the resultant increase persisting 1 d (9). Higher serum albumin level was also associated with lower mortality (9). However, availability of canine specific albumin is limited and may be cost prohibitive (Equitech-Bio, Kerrville, Texas, USA). Canine plasma has approximately 25 to 30 g/L albumin and therefore requires large volumes to supply a conservative amount of albumin (15). Human serum albumin is commonly used to treat critically ill human patients, and is therefore readily available for use in dogs.
The use of 25% HSA has been previously evaluated in 64 critically ill dogs, 21 of which had peritonitis of varying etiologies, although the number of those that were septic was not specified (16). Although no conclusions regarding a benefit in septic dogs could be drawn, the study demonstrated that administration of albumin increased albumin levels and systemic blood pressure. The observation that supplementation did not affect morbidity or mortality was discussed, as was the possibility that it decreased hospital stay, although due to study limitations, significant conclusions could not be reported (16). The use of 10% HSA (25% diluted with 0.9% saline) was evaluated in 73 critically ill dogs (17). Twenty were diagnosed with septic peritonitis and received HSA during or following surgery. Though septic peritonitis was the most common diagnosis in the study, those dogs were not evaluated separately so conclusions regarding that particular subset could not be drawn. However, those that survived had significantly higher albumin and total protein (TP) levels and the magnitude of the improvement in their values was greater (17).
In human medicine the use of albumin infusions continues to be debated. The SAFE (Saline versus Albumin Fluid Evaluation) trial determined that severely septic patients had a lower risk of death with albumin supplementation, suggesting that albumin may have some benefit in this subset of critically ill patients (18). In an effort to establish more specific guidelines for albumin use in critically ill patients, studies with narrow inclusion criteria and outcome measures assessing specific conditions have been carried out. Albumin supplementation has been a focus of research in patients with spontaneous (primary) septic peritonitis resulting from cirrhosis of the liver (19–23). Administration of albumin in addition to antibiotics and other standard therapy lowered the risk of renal injury and improved mortality rate (19,20,24). Another study concluded that in contrast to hydroxyethyl starch, albumin improves systemic hemodynamics due to both volume expansion and effects on peripheral arterial circulation (23). Several studies confirmed that in high risk patients with spontaneous bacterial peritonitis, albumin treatment reduces mortality (21,22,24). Spontaneous (primary) peritonitis is characterized by an infection of the peritoneal cavity with no identifiable source. The mortality rate in dogs is high (53%), similar to that of secondary septic peritonitis (25). In human patients with severe sepsis as a result of secondary septic peritonitis (26), the most common type of septic peritonitis diagnosed in dogs, a beneficial effect was found in patients whose baseline serum albumin was severely decreased. It has further been established that supplemental albumin attenuates the effects of inflammatory cytokines and neutrophil infiltration in animals with septic peritonitis (27). Two studies evaluating 25% albumin supplementation in rats with sepsis secondary to experimentally induced bacterial peritonitis concluded that HSA protects the liver, potentially preventing or reducing subsequent liver failure, and attenuates intestinal and lung injury (27,28). Based on these human and experimental animal studies the use of albumin in specific populations such as dogs with septic conditions, particularly septic peritonitis, may prove to have important clinical benefits.
To the authors’ knowledge, there are no published data comparing dogs with a similar disease (septic peritonitis) which received HSA supplementation to those which did not. The purpose of this study was to describe the use and the effects of 25% HSA on serum albumin levels, COP, TP, duration of hospital stay, and mortality rate in dogs managed for septic peritonitis compared to dogs with septic peritonitis managed without HSA supplementation and to determine whether these parameters improved with albumin supplementation.
Materials and methods
Medical records of dogs presenting to a university teaching hospital between May 2002 and April 2005 were retrospectively evaluated following a search for pharmacy dispension of HSA, and/or a surgical fee code for intestinal resection and anastomosis or abdominal exploratory surgery. A diagnosis of septic peritonitis was established by peritoneal culture intra-operatively and/or abdominocentesis with cytologic evaluation for the presence of bacteria. Inclusion criteria were a diagnosis of septic peritonitis, hypoalbuminemia at the time of diagnosis, definitive surgery for correction of the cause of peritonitis, and management without postoperative open or closed peritoneal drainage. Patients were excluded if the records did not have COP, albumin, or TP recorded, or if the diagnostic parameters or the management criteria listed were not met.
The following were recorded from each report: body weight, surgical exploratory diagnosis, intravenous fluid management prior to initial blood tests (if any), initial total serum protein (iTP) and repeat total serum protein (rTP), initial albumin (iA) and repeat albumin (rA), initial colloid osmotic pressure (iCOP) and repeat colloid osmotic pressure (rCOP), the total dose of HSA if administered [mL/kg body weight (BW)], the duration of HSA administration, the dosage of hydroxyethyl starch 6%/600/0.7 (HES), fresh frozen plasma (FFP), or packed red blood cells (pRBC) if administered (mL/kg BW), length of hospitalization, and survival to discharge. Measurements of COP were made with a commercial colloid osmometer (420 Colloid Osmometer; Wescor, Princeton, New Jersey, USA). All of the initial values represent those recorded prior to HSA supplementation (HSA group) and were obtained from laboratory chemistry panels. The repeat values followed the initial HSA administration (HSA group) or were at varying intervals (last recorded value in non-HSA group) during hospitalization.
Statistical methods
Statistical analyses were performed using SAS statistical software, version 9.2 (SAS Institute, Cary, North Carolina, USA) with significance set at P < 0.05. A mixed linear model analysis of variance (ANOVA) determined significant differences in absolute values of albumin (iA, rA), TP (iTP, rTP), and COP (iCOP, rCOP) between the HSA and the non-HSA group. A mixed linear model ANOVA determined significant differences between the absolute values (iA, rA, iTP, rTP, iCOP, rCOP) within each group. The ANOVA determined association between length of hospitalization and iA, rA, ΔA, iTP, rTP and ΔTP. A t-test determined significant difference in change in albumin
change in TP
and change in COP
between the HSA and non-HSA group. A t-test determined significant differences in iA, rA, ΔA, iTP, rTP, ΔTP, between the surviving and non-surviving groups. Chi-square analysis determined if there was a significant association between HSA supplementation and survival, and if there was a significant association between repeat albumin levels and HSA supplementation. The t-tests determined if there was a significant association between HSA supplementation and length of hospitalization. Chi-square analysis determined significant differences between the HSA and non-HSA group for the percentage of patients supplemented with HES, FFP, and pRBC. A t-test determined significant difference in the mL/kg BW dosage of HES, FFP, and pRBC between the HSA and non-HSA groups.
Outcome measures included survival versus non-survival and the relationship with HSA supplementation, iA, rA, iTP, rTP, ΔA, and ΔTP. We also evaluated length of hospitalization and its relationship with HSA supplementation, iA, rA, iTP, rTP, ΔA, and ΔTP. Additionally, these parameters (iA, rA, iTP, rTP, ΔA, and ΔTP) as well as iCOP, rCOP, and ΔCOP were compared between the HSA group and the non-HSA group. Initial albumin (iA), iTP, and iCOP absolute values were compared to their later repeat absolute values for the HSA and non-HSA groups separately to determine change over time within each treatment group. Initial TP, iA, iCOP, the percentage of patients that received other colloids and the dosage of each colloid were also compared between the treatment groups to establish baseline similarity.
Results
Of 572 records from the database search, 39 met the inclusion criterion and were reviewed. Of the 39 dogs, 18 developed septic peritonitis as a result of dehiscence of a previous enterotomy or intestinal resection and anastomosis site. Of these 18 dogs, 8 had septic peritonitis that resulted from dehiscence of enterotomies for foreign body removal and 10 from dehiscence of an intestinal resection and anastomosis site. Five of these intestinal resections were performed due to a perforating foreign body and the remaining 5 had the resection for undocumented reasons. Seventeen of the 18 dogs with dehiscence had their initial surgery performed elsewhere prior to presentation. One resection and anastomosis was performed at our hospital for reasons that were not noted in the record. The remaining 21 cases included 1 each of gastric ulcer perforation, mesenteric torsion, ruptured stump pyometra, post-operative liver lobectomy, ruptured prostatic abscess, post-operative liver lobectomy and jejunocolic resection and anastomosis, post-operative inguinal hernia repair, post-operative gastrotomy dehiscence (for biopsy), hemoabdomen; 2 splenic torsions, 1 of which was ruptured, 3 perforated gastrointestinal tracts secondary to foreign body, 3 bile peritonitis/gall bladder ruptures, and 4 ruptured pyometra. Of the 39 dogs, 22 received intravenous HSA supplementation (HSA group) as a constant rate infusion and 17 did not (non-HSA group). Of the 39 dogs, 18 survived until discharge from the hospital (Table 1) and 21 were either euthanized (14 dogs) or died (7 dogs) following respiratory/cardiac arrest (Table 2) as a result of their disease (54% mortality). Thirteen of the 21 non-survivors received HSA supplementation (8 euthanized), and 8 of the 21 non-survivors did not receive HSA (6 euthanized). Fourteen breeds of dog were represented.
Table 1
Survivor information including repeat albumin values in descending order with corresponding treatment group and surgically diagnosed cause for septic peritonitis
| Cause of septic peritonitis | Repeat albumin (g/L) | HSA or non-HSA |
|---|---|---|
| Enterotomy dehiscence | 37 | HSA |
| Enterotomy dehiscence | 37 | HSA |
| Gall bladder rupture | 31 | HSA |
| Ruptured splenic torsion | 30 | HSA |
| Gall bladder rupture | 28 | HSA |
| Post-op liver lobectomy and jejunocolic R&A | 26 | HSA |
| Ruptured pyometra | 25 | non-HSA |
| Ruptured pyometra | 24 | HSA |
| Perforated GI FB | 23 | non-HSA |
| Hemoabdomen | 23 | non-HSA |
| Splenic torsion | 21 | HSA |
| Ruptured pyometra | 21 | HSA |
| Enterotomy dehiscence | 21 | non-HSA |
| Ruptured pyometra | 20 | non-HSA |
| Ruptured stump pyometra | 19 | non-HSA |
| Enterotomy dehiscence | 18 | non-HSA |
| Ruptured prostatic abscess | 16 | non-HSA |
| Enterotomy dehiscence | 11 | non-HSA |
R&A — Resection and anastomosis; GI — Gastrointestinal; FB — Foreign body.
Table 2
Non-survivor information including repeat albumin values in descending order with corresponding treatment group, surgically diagnosed cause for septic peritonitis, and cause of death
| Cause of septic peritonitis | Repeat albumin (g/L) | HSA or non-HSA | Euthanasia or Arrest |
|---|---|---|---|
| Perforated GI FB | 32 | HSA | Euthanasia |
| R&A dehiscence (FB) | 29 | HSA | Euthanasia |
| Enterotomy dehiscence | 28 | non-HSA | Euthanasia |
| R&A dehiscence | 24 | HSA | Euthanasia |
| R&A dehiscence | 23 | HSA | Arrested |
| Perforated GI FB | 22 | HSA | Arrested |
| Post-op liver lobectomy | 22 | HSA | Euthanasia |
| R&A dehiscence (FB) | 21 | HSA | Arrested |
| Enterotomy dehiscence | 21 | non-HSA | Arrested |
| Mesenteric torsion | 19 | HSA | Euthanasia |
| R&A dehiscence (FB) | 19 | HSA | Arrested |
| R&A dehiscence | 19 | HSA | Euthanasia |
| R&A dehiscence | 19 | HSA | Euthanasia |
| R&A dehiscence (FB) | 18 | non-HSA | Euthanasia |
| Enterotomy dehiscence | 18 | non-HSA | Euthanasia |
| Gastric ulcer perforation | 17 | HSA | Arrested |
| Gastrotomy dehiscence | 16 | non-HSA | Euthanasia |
| Gall bladder rupture | 15 | non-HSA | Arrested |
| Post-op inguinal hernia repair | 12 | non-HSA | Euthanasia |
| R&A dehiscence (FB) | 12 | non-HSA | Euthanasia |
| R&A dehiscence | 8 | HSA | Euthanasia |
R&A — Resection and anastomosis; GI — Gastrointestinal; FB — Foreign body.
Survivors versus non-survivors
Repeat albumin values were significantly different (P = 0.04) between survivors (mean: 23.9 g/L +/− 1.6, range: 11 to 37 g/L) and non-survivors (mean: 19.7 g/L +/− 5.7, range: 8 to 32 g/L). There was no significant difference between any other variable (iA, iTP, ΔA, ΔTP, rTP) when comparing survivors and non-survivors (P = 0.5, P = 0.08, P = 0.28, P = 0.9, P = 0.25, respectively). There was no significant association between HSA supplementation and survival (P = 0.45) (Table 3).
Table 3
Statistical values of the investigated parameters for survivors and non-survivors
| Survivors | Non-survivors | P-value | |
|---|---|---|---|
| Initial albumin (g/L) | 22a +/− 7.4b, 15–43c | 20a +/− 6.1b, 10–32c | 0.5 |
| Repeat albumin (g/L) | 23.9a +/− 6.7b, 11–37c | 19.7a +/− 5.7b, 8–32c | 0.04d |
| Initial TP (g/L) | 55.8a +/− 13.6b, 32–77c | 48.5a +/− 11.9b, 27–67c | 0.08 |
| Repeat TP (g/L) | 50a +/− 9.1b, 37–65c | 46.1a +/− 11.5b, 27–68c | 0.25 |
| Change in albumin (g/L) | +1.8a +/− 1.8b, −20–+20c | −1.1a +/− 8b, −13–+17c | 0.28 |
| Change in TP (g/L) | −5.8a +/− 12.3b, −34–+19c | −2.3a +/− 11.7b, −26–+26c | 0.9 |
TP — total serum protein;
HSA versus non-HSA
Repeat albumin values were significantly higher (P = 0.01) in the HSA group (mean: 24 g/L +/− 6.8, range: 21.3 to 26.7 g/L) than the non-HSA group (mean: 18.5 g/L +/− 4.7 g/L, range: 15.4 to 21.6 g/L). Repeat TP values were significantly higher (P = 0.01) in the HSA group (mean: 51.9 g/L +/− 9.4, range: 47 to 56 g/L) than the non-HSA group (mean: 42.8 g/L +/− 9.8, range: 37 to 48 g/L). There was a significant difference between groups for ΔA (P = 0.02) (HSA mean: + 3 g/L +/− 7.9, range: −13 to +20 g/L, non-HSA mean: −3 g/L +/− 8.6, range: −20 to +17 g/L). No other variables (iA, iTP, iCOP, rCOP, ΔTP, ΔCOP) were significantly different between the HSA and non-HSA groups (P = 0.64, P = 0.06, P = 0.26, P = 0.82, P = 0.5, P = 0.9) (Table 4). There was no significant difference in the length of hospitalization between the HSA and non-HSA groups (mean: 4.5 d +/− 2.2, mode: 4.0 d, range: 2 to 13 d, P = 0.3). There was no significant association between HSA supplementation and survival (P = 0.45).
Table 4
Statistical values of the investigated parameters for HSA and non-HSA groups
| HSA | Non-HSA | P-value | |
|---|---|---|---|
| Initial albumin (g/L) | 21a +/− 5.7b, 10–32c | 21.9a +/− 7.9b, 11–43c | 0.64 |
| Repeat albumin (g/L) | 24a +/− 6.8b, 21.3–26.7c | 18.5a +/− 4.7b, 15.4–21.6c | 0.01d |
| Initial TP (g/L) | 55a +/− 11.6b, 35–74c | 48a +/− 14.2b, 27–77c | 0.06 |
| Repeat TP (g/L) | 51.9a +/− 9.4b, 47–56c | 42.8a +/− 9.8b, 37–48c | 0.01d |
| Initial COP (mmHg) | 12.8a +/− 2.2b, 6.9–16.7c | 14.5a +/− 1.5b, 12.4–16.7c | 0.26 |
| Repeat COP (mmHg) | 18.6a +/− 4.0b, 12.6–29.1c | 18.2a +/− 5.7b, 12.8–25.9c | 0.82 |
| Change in albumin (g/L) | +3a +/− 7.9b, −13–+20c | −3.3a +/− 8.6b, −20–+17c | 0.02d |
| Change in TP (g/L) | −3a +/− 10b, −25–+19c | −5a +/− 14b, −34–+26c | 0.5 |
| Change in COP (mmHg) | +5.8a +/− 4.5b, −1.3–16.4c | +3.4a +/− 5.8b, −1.7–9.9c | 0.9 |
| Duration of hosp. stay (days) | 4.5a +/− 2.2b, 2–13c | 4.7a +/− 1.7b, 2–8c | 0.3 |
COP — colloid osmotic pressure; HSA — human serum albumin; TP — total serum protein;
Initial values (absolute values compared between groups)
All but 3 patients’ initial values were obtained prior to medical intervention at our hospital. Those 3 patients were in the HSA group and received IV crystalloid fluid therapy prior to initial blood sample collection. Initial albumin, iTP, and iCOP were not significantly different between the HSA and non-HSA groups (P = 0.64, P = 0.06, P = 0.26, respectively). Neither iA or iTP was associated with the length of hospitalization (P = 0.46, P = 0.43, respectively). Initial albumin and iTP were not significantly different between survivors and non-survivors (P = 0.55, P = 0.08, respectively).
Repeat values (absolute values compared between groups)
Repeat albumin and rTP were significantly different between the HSA and non-HSA groups (P = 0.01, P = 0.01, respectively). Repeat albumin and rTP were not associated with the length of hospitalization (P = 0.48, P = 0.99, respectively). Repeat albumin was significantly associated with HSA administration (P = 0.01).
Initial values with respect to repeat values within groups (as change over time within each group)
The HSA group had a significant increase between iCOP (12.8 mmHg +/− 0.7, range: 11.4 to 14.2 mmHg) and rCOP values (18.6 mmHg +/− 0.73, range: 17.1 to 20.1 mmHg) (P < 0.0001). When comparing iA to rA for the HSA and non-HSA groups there was no significant difference (HSA P = 0.09, non-HSA P = 0.1). There was no significant difference between the iTP and rTP for either the HSA or non-HSA group (HSA P = 0.23, non-HSA P = 0.08).
Administration of HSA, synthetic colloids, and/or blood products
Twenty-two dogs received HSA supplementation with a mean dose of 10.2 mL/kg BW +/− 6.6, range: 3.8 to 25.5 mL/kg BW. The mean duration of HSA administration was 39.2 +/− 23.8 h, range: 11 to 98 h. There was no significant difference in the number of dogs receiving HES, FFP, or pRBC between the HSA and non-HSA groups (P = 1.0, P = 0.29, P = 0.33, respectively). Sixteen dogs in the HSA group and 14 in the non-HSA group received HES (mean: 32 mL/kg BW +/− 29.3, range: 1.9 to 100.4 mL/kg BW, mean: 46.9 mL/kg BW +/− 22.5, range: 16.1 to 65.5 mL/kg BW, respectively). There was no significant difference in dosage of HES between the HSA and non-HSA groups (P = 0.12). Seventeen dogs in the HSA group and 13 in the non-HSA group received FFP (mean: 17.3 mL/kg BW +/− 12.25, range: 6.4 to 54.3 mL/kg BW; mean: 25.9 mL/kg BW +/− 17.3, range: 10 to 70 mL/kg BW, respectively). There was no significant difference in dosage of FFP between the HSA and non-HSA groups (P = 0.14). Three dogs in both groups received pRBC (HSA mean: 10.8 mL/kg BW +/− 1, range: 9.6 to 11.7 mL/kg BW; non-HSA mean: 16.3 mL/kg BW +/− 15.5, range: 5 to 34 mL/kg BW). There was no significant difference in dosage of pRBC between the HSA and non-HSA groups (P = 0.59). One dog in the HSA group was administered hemoglobin glutamer — 200 (bovine) (Oxyglobin; Biopure, Cambridge, Massachusetts, USA) at a dose of 3.9 mL/kg BW.
Length of hospitalization
There was no significant association between length of hospitalization and any of the variables [iA, iTP, rA, rTP, ΔA, ΔTP, or HSA status (P-values above)]. Mean length of hospitalization was 4 d +/− 2.2 d, mode 4 d, range 2 to 13 d.
Discussion
In the present study, the HSA group had significant increases in COP, absolute repeat albumin and repeat TP values, and a significantly different change in albumin (rA-iA) compared to the non-HSA group. Also there was a significant association between an increase in albumin and HSA supplementation. Further, repeat albumin values were significantly higher in those that survived. In spite of these findings, HSA supplementation alone did not significantly impact survival.
Human serum albumin supplementation had a significant positive impact on COP and albumin level. The magnitude of change in COP in the group supplemented with HSA was 5.8 mmHg. An elevation of COP by 3.7 mmHg was previously reported (17) following administration of 10% HSA to critically ill dogs, but it is not possible to compare these results with those of the present study. Different concentrations of HSA were evaluated between the studies and the earlier study (17) did not discuss the use of other synthetic colloids in its population. The dose of HSA administered herein was highly variable but both groups received similar dosages of HES. The administration of HES increases COP (29) and may explain the statistically insignificant increase in COP of the non-HSA group (Table 4). However, HES does not provide the functions specific to albumin. The delivery of a lower fluid volume in the form of albumin containing solutions that result in an increased COP may decrease the development of secondary complications including peripheral edema and acute respiratory distress syndrome (30,31). Healing and function of the gastrointestinal tract is also dependent upon albumin (32). Gastric and intestinal edema, prolonged gastric emptying, and ileus have been documented in dogs with experimentally induced hypoalbuminemia (33). Intravascular albumin depletion is a known complication for human surgical patients and progresses with prolonged surgeries (34,35). Sepsis, especially in the peritoneal cavity, is particularly likely to be associated with hypoalbuminemia and decreased COP (34,36). This may be of particular concern in patients undergoing gastrointestinal surgery with concurrent septic peritonitis.
Human serum albumin supplementation did not have a direct positive relationship with survival in the present study. Case numbers were limited to the time period selected and sample size calculation was not performed as part of the study design. Post hoc analysis determined that 94 dogs would have been needed in each group to give the study a power of 80% and significance level of 5% to determine an effect on survival. The albumin value subsequent to supplementation or last recorded albumin level during hospitalization was significantly higher in those that received HSA. A recent publication established that canine patients surviving until discharge following surgery for septic peritonitis had higher final albumin levels than those that did not survive (9). This finding was supported in the present study. All of the dogs herein were hypoalbuminemic and there was no difference in the baseline value of albumin between the treatment groups. Therefore, an effect of preoperative hypoalbuminemia on survival could not be determined. Establishing preoperative albumin level as a predictor for mortality in dogs with septic peritonitis has been challenging (5,10,12), although it has been established that preoperative hypoabluminemia, and a diagnosis of preoperative septic peritonitis increase the risk of septic peritonitis (or recurrent septic peritonitis) in patients undergoing gastrointestinal surgery (4,12).
Secondary generalized peritonitis, usually caused by bacteria, is the most common form of peritonitis in dogs. Leakage from the gastrointestinal tract, often as a result of surgical wound dehiscence, is the most common cause (37). Other causes include gastrointestinal foreign bodies, intussusceptions, gastric dilatation-volvulus, abdominal abscesses (pancreatic, prostatic), ruptured uterus secondary to pyometra, necrotizing cholecystitis, and gall bladder perforation, rupture or necrosis (6–8,10,37). The causes of septic peritonitis in the present study were consistent with previous studies (6–8,10,37). Of the dogs in this study 41% (16/39) developed septic peritonitis secondary to the presence of, or subsequent to, removal of a foreign body. Of these 16 dogs, 81% (13/16) resulted from dehiscence at the enterotomy or resection and anastomosis site. It would have been interesting to investigate this subset of dogs further in regard to pre-dehiscence albumin status and medical intervention. However, these dogs had initial surgery elsewhere, and information regarding care prior to presentation was limited. The mortality rate of dogs with septic peritonitis in this study (54%) is similar to previous reports (6–8,10). Of the 21 dogs with intestinal leakage as a result of dehiscence or perforating foreign body, 6 survived. Twelve of the 21 dogs were in the HSA group. A 47% to 63% mortality rate has previously been reported in dogs with septic peritonitis as a result of gastrointestinal leakage (11,38). Evaluating the studied variables, including mortality, relative to the underlying cause for septic peritonitis was beyond the scope of the present study.
Peritoneal drainage may be reserved for cases in which contamination is considered severe or if the source of contamination cannot be identified and controlled at the time of surgery. In an effort to avoid confounding factors contributing to duration of hospitalization, protein level differences, and mortality, only dogs managed with a closed abdomen were included in the present study. Hypoproteinemia is a reported complication associated with open peritoneal drainage in both humans and dogs (7,10,39,40). The surgical management of human and veterinary patients with septic peritonitis has been evaluated in a number of studies. Lower mortality rate was associated with the use of a “closed abdomen” technique compared with an “open abdomen” technique (31% versus 44%) in 1 human study. Additionally, hypoalbuminemia was an independent factor associated with death and re-operation (41). In an earlier veterinary study, 7 of 25 (28%) dogs and cats managed with open peritoneal drainage developed hypoproteinemia and the overall mortality rate was 48% (7). In a subsequent veterinary study investigating dogs and cats with septic peritonitis, in which surgical management (open versus closed) varied, all subjects developed hypoalbuminemia (10). Indicators of a poor prognosis included refractory hypotension, cardiovascular collapse, disseminated intravascular coagulation, or the development of respiratory disease. Although hypoalbuminemia was not an independent indicator for a worse prognosis, it contributed to the development of acute lung injury, pulmonary edema, and pleural effusions. Clinical evidence of respiratory dysfunction afforded a worse prognosis and has been demonstrated previously (10,42). Closed suction drains have been described in the management of septic peritonitis in dogs (43) with no difference in reported mortality rate. However, their use may contribute to the development of nosocomial infections (43) and their contribution to the development or persistence of post-operative hypoproteinemia and hypoalubminemia remains unknown.
Renal impairment as a result of hypotension, intraoperative hypotension, and the need for postoperative vasopressor therapy have been implicated as causes of death in dogs with septic peritonitis (5,10). Albumin supplementation has been reported to increase blood pressure in veterinary patients that are critically ill (9,16). Although beyond the scope of the present study, it would have been interesting to determine if there was a significant difference in blood pressure between the groups, whether hypotension affected survival, and whether albumin level played a role in the need for re-operation or recurrent septic peritonitis. It has been suggested in the human literature that HSA supplementation be reserved for “high-risk” patients or those severely hypoalbuminemic as a result of septic peritonitis (21,26,44). Perhaps a study that stratifies treatment groups in a similar manner would identify a survival difference between treatment groups. Additionally, a prospective study would potentially be able to determine a significant effect of different dosages and/or concentrations of HSA supplementation on several parameters in these dogs.
Limitations of the present study include its retrospective nature, the low number of dogs, and the variable dosage of HSA. In an effort to define a control group, dogs with the same diagnosis (septic peritonitis) and similar surgical management (closed abdomen) that did not receive HSA supplementation were compared to a comparable population that did receive HSA. Initial values of albumin, TP, and COP were compared between the supplemented and non-supplemented groups in order to establish baseline similarity between the treatment groups and there was no significant difference in these parameters. Additionally, the number of dogs administered each type of colloidal supplementation or blood product other than HSA and the dose was also compared to establish similarity between the treatment groups. There was no significant difference between the numbers of dogs administered these supplemental fluids in the HSA and non-HSA groups, nor was there a significant difference between the administered dose of these fluids. Survival rate is difficult to interpret retrospectively as dogs that would have otherwise survived may have been euthanized or have resuscitative attempts ceased following cardiopulmonary arrest due to financial constraints or owner decision. Length of hospital stay can also be misinterpreted if there were more critically ill dogs that required a longer hospital stay but survived until discharge from the hospital. These factors may have contributed to failure to detect an association between HSA administration itself and survival or length of hospital stay, in spite of other significant findings.
While healthy dogs are at higher risk of complications associated with HSA supplementation (45,46) the immune-dysfunction in critically ill dogs is thought to provide a protective effect by reducing antibody production associated with transfusion (17,47–49). The development of a type III hypersensitivity reaction has been confirmed in 2 critically ill dogs administered HSA. The reaction occurred within 16 d and both successfully responded to treatment (50). Therefore, the benefits of HSA administration should be thoughtfully considered for use in selected canine patients and clients should be advised regarding appropriate monitoring and follow-up care.
To the authors’ knowledge, this is the first description of HSA supplementation in critically ill, hypoalbuminemic dogs with septic peritonitis, compared to dogs with septic peritonitis which did not receive HSA. The results of the present study suggest that albumin supplementation increases albumin levels, TP, and COP in canine patients with septic peritonitis. Additionally, higher postoperative albumin levels are associated with survival. The ability of albumin transfusions alone to specifically improve the outcome in dogs with septic peritonitis should be investigated prospectively. CVJ
Footnotes
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