EFFICIENCY OF THE CRITERIA OF INITIATION OF RENAL REPLACEMENT THERAPY IN PATIENTS WITH POLYTRAUMA COMPLICATED BY MULTIPLE ORGAN DYSFUNCTION SYNDROME
Regional Clinical Center of Miners’ Health Protection,
Leninsk-Kuznetsky, Russia
The specific feature of the modern rates of injuries is the high proportion of multiple, associated injuries and polytrauma which are characterized by high mortality and disability [1, 3, 4, 9, 11, 12, 17). The main cause of lethal outcomes is development of various disorders of organ functions in patients with polytrauma, with the rate (according to the data from different authors) of 20-98 %; the high proportion is acute functional insufficiency of two and more organs or their systems [1, 3, 5, 7, 10, 14].
The triggering mechanism for multiple organ dysfunction syndrome (MODS) and its earlier phase – systemic inflammatory response syndrome (SIRS) – is lesion of the cells by multiple inflammatory mediators releasing from the immune competent cells, which are exposed to traumatic, ischemic, hypoxic, infectious or other inducing action. The developing “mediator cytokine storm” and systemic inflammatory response cause and subsequently worsen the energetic deficit in the organ cells and become the factor of initiation and progression of MODS [1, 2, 5, 10, 14]. The clinical course of MODS is worsened by presence of the infectious process [2, 15, 16]. Treatment of patients with polytrauma is a complex problem. In case of late diagnosis, MODS is accompanied by longer duration, significant economic losses and lethal outcomes.
Commonly, three directions of treatment (depending on pathogenesis) are separated. The first direction is elimination of action of a triggering factor or disease, which initiates or supports the aggressive influence on the body (trauma, blood loss, severe hypovolemia, pulmonary hypoxia, severe invasive infection, pulmonary destruction etc.). The second one is correction of disorders of oxygen balance including restoration of oxygen transport function of the blood, therapy of hypovolemia and hemoconcentration, correction of disorders of hemorheology. The third direction is replacement (even temporary) of the function of an injured organ or system by means of pharmaceutical or instrumental methods [1, 2, 3].
As a part of intensive care of MODS in patients with polytrauma, the extracorporeal techniques acquire the very important role as efficient replacement therapy, the method for correction of rude metabolic disorders, detoxication. But also one considers the possibilities for using the new properties of the modern dialyzers/hemofilters with abilities to selective decrease in the levels of cytokines and removal of endotoxins in the blood [5, 6, 8, 10].
Currently, there are techniques for estimation of severity of injuries to individual organs and systems, for example, calculation of respiratory index (Pao2/FiO2), renal index, Glasgow Coma Scale, acid-base balance, water-electrolyte composition of the blood, level of lactate, bilirubin and creatinine in the serum of arterial and venous blood etc. The following ways of integral estimation of the severity of patients’ condition were used: the indices (scales) ISS, TISS, APACHE, Military Field Surgery-State at Admission, Military Field Surgery-Condition in Hospital, SAPS, SOFA, MODS [1, 3, 9, 12-16]. However these techniques (even their combination) do not allow performing early diagnostics and prediction of multiple organ dysfunction syndrome and visceral complications in patients with polytrauma.
There is an actual issue about the criteria determining the timeliness of initiation of renal replacement therapy [2, 3, 6, 8]. The common values, such as oligoanuria (the rate of diuresis < 200 ml/12 h), hyperkalemia (level of potassium > 6.5 mmol/l), severe acidosis (blood pH < 7.1), azotemia (urea > 30 mmol/l), severe disnatriemia (level of natrium < 160 mmol/l), suppose the initiation of renal replacement therapy at the stages of persistent organ insufficiency, when excretive function of the kidneys is almost lost and the development of evident water-electrolytic disorders is noted. Persistent hyperkalemia, hypernatriemia and decompensated metabolic acidosis lead to disordered myocardial function, ARDS and vasoplegia that required intensive respiratory and inotropic support. The use of the technique of renal replacement therapy is inevitable and, at the same time, extremely dangerous in conditions of persistent disorders of vital functions of the body.
The objective of the study – to determine and to estimate the efficiency of the offered criteria of initiation of intermittent renal replacement therapy (RRT) in patients with polytrauma complicated by multiple organ dysfunction syndrome (MODS).
MATERIALS AND METHODS
The study is based on the retrospective and prospective analysis of the treatment results in the patients with MODS as result of polytrauma. The patients received the treatment in the intensive care unit in Regional Clinical Center of Miners’ Health Protection in 2011-2015. The study was reviewed during the session of the ethical committee of the center. The written consents from the patients and their relatives were received. The study included 29 retrospectively reviewed cases and 42 patients who were distributed into two groups.
The inclusion criteria were:
- polytrauma (ISS < 35);
- age > 18 and < 60;
- multiple organ dysfunction (dysfunction of two or more organs or systems).
The exclusion criteria were:
- patients in agonal state;
- severe TBI (level of consciousness with GCS < 8);
- concurrent pathology in the stage of decompensation.
Randomization was conducted with the computer program with the limited database of random numbers.
The odd numbers corresponded to inclusion of a patient into the study group – 22 patients, the even numbers – the comparison group, 20 patients (the table 1). The mean age was 38.5 ± 3.8. The men/women ratio was 33/9 (78.4 % / 21.65 %) correspondingly. Both groups included the patients with polytrauma complicated by MODS, with acute renal insufficiency as a dominating component. The groups were similar in relation to the severity of the injuries estimated with ISS (Injury Severity Score).
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Table 1 |
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| The general characteristics of the groups. | ||
| Groups | Comparison group | Main group |
| Amount of patients | 20 | 22 |
| Gender: male/female | 16/4 | 17/5 |
| Age (years) | 38.5 ± 3.8 | 35.8 ± 2.1 |
| ISS (points) | 38 ± 1.2 | 38 ± 1.4 |
During the complex treatment of MODS all patients received the standard complex of intensive care: respiratory support, infusion, antibacterial and rheological therapy. Correction of anemia, acidosis, enteral and parenteral nutrition and renal replacement therapy were conducted according to the indications. The common indications for treatment of acute renal insufficiency were used in the comparison group: oligoanuria (≥ 3 days), blood urea (≥ 30 mmol/l), creatinine (≥ 1,000 mcM/l), hyperkalemia (K+ ≥ 6 mmol/l), metabolic acidosis (pH ≤ 7.2) and increasing hyperhydration.
We reconsidered these parameters in the study group.
As a rule, acute polytrauma is accompanied by development of acute respiratory insufficiency in combination with certain intensity of cardiovascular insufficiency. Elimination of the shock events is accompanied by development of reperfusion syndrome that can initiate worsening the patient’s condition, increasing respiratory insufficiency, cardiovascular insufficiency and appearance of the initial symptoms of acute renal dysfunction.
The following indications for initiation of renal replacement therapy were identified in the retrospective analysis (multiple lineal logistic regression) of 29 cases of polytrauma with complications including multiple organ dysfunction and acute renal insufficiency: achievement or/and exceedance of two or more values relating to the parameters: Na+ ≥ 150 mmol/l, plasma osmolarity ≥ 300 mOsm/l, urea ≥ 20 mmol/l, creatinine ≥ 200 mcmol/l and increase in plasma toxicity according to the level of average molecules ≥ 0.8. These predictors made the highest influence on development of organ dysfunction, β values ≥ 3.48 ± 0.21. Hour diuresis was not the basic criterion for initiating dialysis therapy in the main group; it was of secondary importance.
Regardless of the group, all patients received renal replacement therapy with the device AK-200 ultra (Gambro, Sweden) with the mode of veno-venous hemofiltration, with the average blood flow rate of 180 ± 20 ml/min. The vascular approach was made by means of catheterization of the femoral vein with the dual-lumen catheter. The first session was 1-1.5 hours with the dialyzer 1.4 m2, with the low rate of blood flow. When a patient demonstrated adaptation, the standard mode was initiated. The duration of the procedure was gradually increased to 4-5 hours. The control of the patients’ condition was realized by means of clinical and biochemical monitoring (the main parameters of hemodynamics and diuresis, acid-base balance, water-electrolytic composition of blood plasma, changes in nitric waste) and with the paraclinical techniques (X-ray, endoscopic methods, ultrasonic diagnostics).
The received results were analyzed with Statistica. The logistic lineal regression was used. The probability technique was used for estimation of statistical significance of the equation with calculation of χ2 with the method of confidence intervals.
RESULTS AND DISCUSSION
Severe skeletal injury (blood loss – 1.4 ± 0.3 l) was identified in all cases at the moment of hospital admission, and it combined with closed thoracic, abdominal and traumatic brain injury. The summary value of ISS was without differences. The comparative analysis showed the lower value of GCS (without sedation) in the comparison group at the moment of initiation of renal replacement therapy as compared to the main group (8 ± 0.7 / 9 ± 0.8). The control CT images of the brain showed one or other degree of intensity of cerebral edema in all patients in both groups. The density of the structures was from 40 to 30 HU in 7 patients in the main group and in 3 patients in the comparison group, from 30 to 20 HU in 2 and 7 patients correspondingly. The structure density from 20 to 10 HU (significant degree of cerebral edema) was only in 1 patient in the main group and in 6 patients in the study group.
The control CT images of the chest organs identified ARDS of 2nd degree in 12 patients in the main group at the moment of initiation of renal replacement therapy, ARDS of degrees 2-3 – in 10 patients in the study group. It is necessary to note that 32 patients of both groups (76 %) demonstrated the increase in hypernatriemia, despite of adequate diuretic therapy and preserved rate of diuresis. It is associated with earlier disorder of the concentration function of the kidneys with preserved excretory function.
The estimation of condition with MODS scale was 15.6 ± 2.4 points at the moment of initiation of renal replacement therapy in the main group. It supposes 50 % of mortality. The mean value was 18.9 ± 1.8 in the comparison group, with the probable mortality of 75 %. It is associated with later initiation of renal replacement therapy and development of stronger disorders of hemostasis in the comparison group.
The amount of the procedures of renal replacement therapy was 12.4 ± 0.7 in the comparison group. The excretory function of the kidneys recovered on the day 19 ± 1 from the moment of initiation of renal replacement therapy in 8 patient of this group. Diuresis increased to 107 ± 11 ml per hour. Water-electrolytic and acid balance disorders disappeared. The main parameters of hemodynamics stabilized. The degree of respiratory support decreased.
The mortality was 12 patients (60 % in this group).
For 11 patients of the study group such results could be achieved only with lower number of sessions of hemodialysis and hemodiafiltration (8 ± 0.53 procedures) as compared to the control group. This group demonstrated faster recovery of the renal concentration function and transition to polyuria (14 ± 2 days).
The most significant parameters for making decisions were electrolytic disorders (Na+ in blood plasma) and estimation of osmolarity. The mortality was lower in the study group (7 patients, 38.8 % from total amount of the patients)(the table 2).
| Table 2 | ||
| Results of treatment of patients with polytrauma complicated by MODS in dependance on criteria of initiation of RRT | ||
| Groups | Main group | Comparison group |
| Criteria of initiation | Additional | Generally accepted |
| ALV duration | 17 ± 3 * | 24 ± 4 |
| Amount of IRRT procedures | 8 ± 0.5* | 12 ± 0.7 |
| Duration of ICU stay | 31 ± 4 | 37 ± 2 |
| Duration of hospital stay | 46 ± 2 * | 54 ± 3 |
| Mortality | 55.5 % (persons) | 65 % (persons) |
| * - P < 0.05 as compared with the comparison group. | ||
The clinical case. The patient M., date of birth – December 7, 1985 (28 years), a driver. The emergency team transported him to the admission department of Regional Clinical Center of Miners’ Health Protection after a road accident (frontal collision). The diagnosis was: “Severe associated injury, brain concussion, closed chest injury, non-complicated fractures of the ribs 3 and 4 to the right and 7-8 to the left, a fracture of the left femoral bone with displacement, a fracture of the right humerus”.
At the moment of admission the patient was in severe condition determined by polytrauma and the course of traumatic shock. The patient was in consciousness, but hyposthenic, retarded and with low ability to efficient contact. GCS was 12. The pupils were of middle size, in middle position, OD = OS, with photoreactions. The skin was pale and cold. Breathing was independent, through natural airways. Auscultation showed access to all departments, with weakness to the left. SpO2 – 90 % for breathing with air, and 96 % for insufflation of resuscitation oxygen (4-6 l/min). Hemodynamics was stable with trend to hypotonia with arterial pressure of 85-90/55-60 mm Hg. The anti-shock measures were continued in the admission department of the intensive care unit (tracheal intubation, ALV with IPPV, FiO2 – 0.6, Fr – 15, infusion-transfusion hemostatic therapy, acidosis correction). The surgery was conducted after the examination (laparotomy, revision of the abdominal organs). A splenic injury was identified (splenectomy, hemostasis). Beller splint was applied for the left lower extremity. A fracture of the right humerus in the distal one-third was identified in the surgery room. Closed reposition and plaster immobilization for the right humerus were performed. The patient was transferred to the intensive care unit.
The diagnosis at the moment of admission to ICU: “Polytrauma. Closed traumatic brain injury, brain contusion of middle severity. Bruise of soft tissues of the head. A closed chest injury, a non-complicated fracture of the left ribs 3, 4, 5, 6, 7, 8, 9. Left lung contusion, contusion of the lower lobe of the right lung. Minimal hydrothorax on both sides. A closed abdominal injury with splenic injury. A closed fracture of the right humerus in the distal one-third. A closed transverse comminuted fracture of the right femoral bone on the border of the proximal and middle one-third. Traumatic shock of degree 2”.
The clinical course of shock was arrested within the first 24 hours. Afterwards, the period of relatively stable condition was noted. Despite the intensive care, the negative trends were noted on the days 9-10. Hyperthermia to febrile values was noted. The laboratory examination: increasing leukocytosis up to 27 × 109 with stab shift leftwards. The chest X-ray examination showed the development of bilateral aspiration and polysegmentary pneumonia. Destruction in the region of the lower lobe of the left lung. The left pleural cavity draining was conducted, Bulau pleural drain was placed into 7th intercostal space. Each day the pleural cavity was irrigated with solutions of antiseptics.
On the day 11 after the injury the patient’s condition was extremely severe, determined by sepsis, bilateral aspiration, polysegmentary pneumonia and appearance of clinical sings of multiple organ dysfunction. Respiratory insufficiency was increasing. Hemodynamic instability appeared. Inotropic support was initiated with infusion of dopamine (7-12 µg/kg/min). AP – 100-110/60-70 mm Hg, HR – 110-120 per min. Despite of stimulation with saluretics, a trend to decrease in daily diuresis was observed. The laboratory examination showed anemia of middle severity, leukocytosis with stab shit leftwards, the level of nitric waste in the blood – at the upper limit of the normal value. Na+ - 164 mmol/l, osmolarity – 306 mOsm/l.
Considering the negative course of the patient’s condition, the decision about initiation of renal replacement therapy was accepted. There were total of 7 sessions of hemodiafiltration with GAMBRO AK 200 ultra S. The procedures were conducted according to the veno-venous contour (with dual-lumen catheter) with the bicarbonate dialysate. The duration was 2-4 hours. The dosed heparinization – 5-8 thousand units. The rate – 180-200 ml/min. 0.7-3 l of ultrafiltrate were removed according to the indications. The main parameters of hemodynamics were stable, with slow trend to normalizing. There were no complications. Laboratory values were estimated each day (the table 3).
| Table 3 | ||||||||||||
| Time course of the laboratory values of the patient M. (age of 28) | ||||||||||||
| Data/value | Day 1 | Day 5 | Day 10 | Day 11 | Day 12 | Day 13 | Day 14 | Day 16 | Day 18 | Day 21 | Day 30 | Day 41 |
| Na | 151.9 | 146.5 | 151.1 | 154.3 | 155.9 | 151.3 | 149.1 | 150.5 | 155.2 | 150.3 | 135.2 | 135.3 |
| K | 4.93 | 4.35 | 4.03 | 3.85 | 4.35 | 3.61 | 3.52 | 2.85 | 2.69 | 3.04 | 4.81 | 3.47 |
| Cl | 112 | 106.1 | 102.6 | 114.5 | 111.5 | 106 | 107.2 | 106.3 | 106.7 | 104.3 | 102.9 | 102.41 |
| Ca | 1.89 | 2.09 | 1 | 1.91 | 1.97 | 1.024 | 1.06 | 1.95 | 0.812 | 0.487 | 1.91 | 1.36 |
| Urea | 4.08 | 4.08 | 8.5 | 17 | 31.9 | 34.9 | 31.8 | 26.8 | 19.9 | 14.7 | 10.1 | 4.7 |
| Cre | 60.7 | 72.9 | 79.4 | 117.1 | 363 | 184.8 | 179 | 103.7 | 85.7 | 62.1 | 62 | 56.6 |
| CM | 0.805 | 0.422 | 0.43 | 0.42 | 0.71 | 0.501 | 0.477 | 0.408 | 0.367 | 0.404 | 0.381 | 0.345 |
| osmolarity | 285 | 274 | 281 | 306 | 308 | 308 | 302 | 295 | 287 | 288 | 283 | 278 |
| pH | 7.215 | 7.365 | 7.31 | 7.353 | 7.384 | 7.371 | 7.395 | 7.412 | 7.367 | 7.375 | 7.42 | 7.398 |
| RBC | 3.84 | 2.8 | 2.86 | 2.83 | 3.51 | 3.28 | 3.17 | 3.02 | 3.43 | 4.04 | 4.06 | 3.55 |
| HCT | 33.1 | 25 | 27 | 28.7 | 34.7 | 32 | 31 | 29.5 | 32.2 | 38.2 | 37.9 | 31.7 |
| HGB | 110 | 85 | 86 | 83 | 98 | 91 | 89 | 86 | 93 | 107 | 111 | 97 |
| PLT | 145 | 136 | 452 | 516 | 492 | 448 | 351 | 355 | 409 | 441 | 389 | 402 |
| WBC | 13 | 12.88 | 27 | 21.99 | 21.49 | 24.34 | 22.3 | 25.09 | 20.87 | 16.64 | 14.56 | 10.8 |
| 1st 2nd 3rd 4th 5th 6th 7th | ||||||||||||
| Hemodiafiltration sessions | ||||||||||||
The condition of the patient was stabilizing at the background of renal replacement therapy: decreasing toxemia, normalizing water-electrolytic composition, acid-base balance and hemodynamics (infusion of vasopressors was cancelled on 16th day), diuresis restoration, normalizing laboratory values. The surgical intervention was performed for removal of the focus of destruction in the left lobe of the right lung (the day 32) and included right-side thoracotomy, atypic resection of the lower lobe of the right lung.
Regression of respiratory insufficiency was noted at the background of intensive care. ALV was cancelled on the day 36 after the moment of admission. The tracheostomy tube was removed in 24 hours.
The condition demonstrated the middle severity on the day 41 after the injury. The patient was conscious, adequate, with good time and space orientation. Breathing was independent, adequate, through the natural airways. SpO2 – 97-98 % for air breathing. Hemodynamics was stable, AP – 110-120/70 mm Hg, HR – 70-76 per min. During palpation the abdomen was soft and painless. Bowel peristalsis was auscultated. Diuresis corresponded to the degree of hydration. The laboratory values were compensated. The patient was transferred to the surgery unit. The hospital treatment lasted for 54 bed-days.
Therefore, early initiation of renal replacement therapy for the patient with polytrauma, which was complicated by severe sepsis and multiple organ dysfunction, allowed fast decrease in the critical level of toxemia, restoration of water-electrolytic balance and prevention of the predicted lethal outcome.
CONCLUSION
Non-corrected hypernatriemia (plasma Na+ ≥ 150 mmol/l) and hyperosmolarity (≥ 300) can be the indications for use of dialysis techniques. These criteria allow earlier initiation of renal replacement therapy that results in reducing amount of necessary procedures for elimination of acute renal insufficiency, persistent stabilization of condition in patients with stabilization, 1.5-fold reduction of mortality, more than 11 % decrease in mortality.