Annals of Burns and Fire Disasters - vol. XI - n. 2 - June 1998

HIGH-VOLUME SLOW CONTINUOUS VENOVENOUS HAEMOFILTRATION IN SEPTIC NONOLIGURIC BURNED PATIENTS

Weksler N., Chorny I., Gurman G.M, Shapira A.-R.

General Intensive Care Unit, Division of Anaesthesiology, Soroka Medical Center
Ben Gurion University of the Negev, Beer Sheva 84101, Israel

SUMMARY. Thirty-two burned patients with an affected surface area varying from 50 to 70% of second- and third-degree burns, fulfilling the Bone criteria for sepsis, and with a urinary output greater than 1 ml/kg/h, were randomly allocated in this study. Exclusion criteria were: previous renal failure (represented by a creatinine blood level higher than 3 mg/dl), documented urinary output less than 0.5 ml/kg for a period of four hours or longer, previous cardiac insufficiency, and chronic pulmonary disease). The severity of the illness was estimated by the APACHE 11 score, and the intensity of treatment by TISS (Therapeutic Intervention Scoring System). The groups were similar for age, gender distribution, APACHE 11 and TISS, and urea and creatinine levels at the beginning of the study. The Pa02/F102 ratio was significantly lower in the C~ (continuous venovenous haernofiltration) group, and showed a marginal improvement with continuous venovenous haemotiltration (CVVH). The fluid balance was negative in the C~ group and positive in the control group. The filtration formation rate ranged from 60 to 90 1 per day. The survival rate was 70% in the study group and 40% in the control group (p < 0.05). In conclusion, high~flow improves survival in septic, nonoliguric, severely burned patients.

Introduction

Since its introduction in the late 70s as an alternative technique for haemodialysis therapy in the critically ill patient, haemotiltration has undergone important con­ceptual modifications.
New indications for the use of this renal replacement technique, such as sepsis, heart failure, pancreatitis and exogenous intoxications, 4 were added in the last years. Sepsis is still a common cause of high mortality and morbidity in critically ill patients, despite the improvement seen in supportive therapies.
The clinical picture of sepsis includes temperature dysregulation, leukocytosis or leukopenia, tachycardia and tachypnea. However, when these signs occur in the absence of infection, the term SIRS (systemic inflammation response syndrome) should be used. Both SIRS and septic syndrome are modulated by mediators released on the insult, such as cytokines, complement factors (C2, C4), platelet-activating factors, and thromboxane and other arachidonic acid metabolites.
SIRS is triggered by a wide variety of insults, including infections, pancreatitis, multiple trauma, haemorrhagic shock, and burns.
Although the incidence of burn injury has declined over the last decade, the mortality rate in major burns with an affected body surface area ranging from 50 to 80% reaches nearly 80%. 
There is a close relationship between the blood level of cytokines and mortality rate in SIRS and septic patients. Experimental studies have shown that continuous haemofiltration has beneficial effects on haemodynamic parameters in septic animals and that this improvement seems to be linked to the filtration volume.
The advantage of a pump-driven haernofiltration system over a continuous arteriovenous haernofiltration (CAVH) system, as shown by Storek and co-authors, was related to the faster elimination of toxic mediators with a molecular weight of 800-1000 daltons by high-volume haemofiltration. The impact of high filtrate volume formation on the survival rate was described in a porcine model of sepsis` in which, despite a zero fluid balance, the survival rate was greater with high volume continuous venovenous haernofiltration (CVVH). This improvement was again attributed to the enhanced clearance of inflammatory mediators.
Burns are associated with a significant release of inflammation mediators. The use of C therefore seems to be logical for decreasing the increased cytokine blood levels, decreasing the inflammatory response. 

Methods

Thirty-two burn patients (affected body surface area 50-70%, second and third degree fulfilling the Bone criteria for sepsis, and with urinary output higher than I ml/kg/h) were randomly allocated in this study. Randomization was effected on the basis of the final ID digit. Exclusion criteria were: previous renal failure (represented by a creatinine blood level higher than 3 mg/dl), documented urinary output less than 0.5 ml/kg for a period of four h or longer, previous cardiac insufficiency, and chronic pulmonary disease. Severity of the disease was estimated by the APACHE 11 score" and intensity of treatment by the Therapeutic Intervention Scoring System (TISS). 
CVVH was performed through two venous 8F catheters (Vygon, France), and a Gambro, dialysis machine (Gambro AK 10, Gambro, Sweden) was used to pump blood in a flow of 200 ml/min through a polyamide hollow filter, with a surface area of 0.66m (Gambro FH 66, Lund, Sweden).
The circuit was rinsed with 3 1 of 0.9% NaCl solution with 5000 units of heparin added per U
A loading dose of 2000 units of heparin was intravenously administered two to three min before blood was allowed to pass into the filter," followed by a continuous infusion into the afferent port of the circuit of 500 units/h. The whole blood clotting time was measured hourly and the heparin rate was adjusted to keep it between 10 and 15 min.
Predilution was achieved by a continuous infusion of Ringers lactate into the afferent limb of the circuit. In both groups, sedation was obtained with a continuous infusion of propofol, and the infusion rate was adjusted to maintain the patients at a Ramsays sedation score of 3. The replacement solution was given as Ringers lactate solution, at a sufficient rate to maintain the desired hourly fluid balance. The patients were maintained in a negative fluid balance by replacing 90 to 95% of the fluid removed (urine or filtrate).
Parenteral nutritional support was similar in both groups, and consisted of a standard solution of amino acids, an energy source of 50% fat and 50% glucose, vitamins, electrolytes, and trace elements according to the daily requirements established by standard formulas.
SAS was used for statistical analysis and a p value < 0.05 was considered significant.

Results

Out of thirty-two patients enrolled in the study, twenty fulfilled the entry criteria, and were grouped in two lots of ten patients each. The groups were similar in age, gender distribution, APACHE score, and TISS.
The plasmatic urea and creatinine levels were similar in the two groups at the beginning of the study, while the Pa02/Fl02ratio was lower in the CVVH group, this value showing a marginal improvement with CVVH.
The survival rate was significantly higher in the CVVH group. The daily fluid balance was negative in the C~ group and positive in the control group. The duration of C treatment was 6.4 + 2.8 days (range, 4 to 13 days). There were no permanent serious CWH-attributable sequels. Table I summarizes the results of both groups.

Conclusions

Severe thermal injuries are followed by a significant increase in serum cytokine levels, mostly IL-6 and alpha­TNR` These substances are involved in SIRS, whic is clinically manifested by temperature dysregulation, tachycardia, tachypnea, leukocytosis or leukopenia.
These manifestations are generally linked to sepsis, which is the systemic inflammatory response syndrome, in the presence of infection.` Cytokines modulate a number of immunological functions following thermal injuries, they may influence the resistance of burns, and their blood levels are inversely related to survival, in this group of patients.
Burn patients are very often attacked by superimposed infections, which aggravate prognosis still further.
Despite the improvements in supportive care in burns, the mortality rate is still very high, reaching nearly 70% when the full-thickness burn area is more than 50% and is associated with respiratory failure.
ARDS is frequently associated with sepsis and SIRS.` The pathogenesis of these phenomena seems to be linked to various mediators of the inflammatory response released in the circulation following the insult.
Haemotiltration has been proposed for the treatment of septic nonoliguric patients with respiratory failure, with a significant improvement in the survival rate? The use of high-flow C~ was previously recom­mended in the treatment of septic patients.
The efficacy of haernofiltration in the removal of inflammatory mediators has recently been reappraised,` and a filtration rate of more than 50 1 a day may be necessary in order to wash out the mediators involved in the inflammation process. In brief, the survival rate of patients with extensive burns (50 to 70%) was significantly increased when high-flow (60 to 90 I/day filtrate production) haernofiltration was used. Whether this improvement is a consequence of the elimination of inflammatory response mediators or of better fluid management is beyond the scope of this investigation and requires further study.

RESUME. Dans cette étude, 322 patients brûlés (surface brûlée 50-70% de brûlures de deuxième et troisième degré), qui répondaient aux critères de Bone pour ce qui concerne la sepsis et qui présentaient une production urinaire supérieure à Iml/kg/h, ont été divisés au hasard. Les critères dexclusion étaient: insuffisance rénale précédente (manifestée par un niveau hématique de la créatinine supérieur à 3 dg/dl), production urinaire documentée inférieure à 0,5 ml/kg pendant une période de 4 h ou plus longtemps, insuffisance cardiaque précédente, ou maladie chronique pulmonaire. La sévérité de la maladie a été évaluée selon le score APACHE Il et lintensité du traitement selon TISS. Les deux groupes étaient comparables pour lâge, la distribution sexuelle, APACHE Il et TISS, et les niveaux durée et de créatinine au commencement de létude. Le rapport PaO2/FI02 étaient significativement inférieur dans le groupe de la filtration vénoveineuse continue (FVVQ et démontrait une légère amélioration avec la FVVC. Le bilan liquide était négatif dans le groupe FVVC et positif dans le groupe témoin. Le taux de la formation de la filtration variait entre 60 et 90 1 par jour. Le taux de survie était 70% dans le groupe détude et 40% dans le groupe témoin (p < 0.05). En conclusion, lhémofiltration vénoveineuse continue à haute circulation améliore la survie dans les grands brûlés septiques et nonoliguriques.

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