Different Fluidic Strategy in Patients With Acute Abdomen : The Sure Volume
Different Fluidic Strategy in Patients With Acute Abdomen : The Sure Volume
Acute abdomen is the clinical manifestation of irritation of the peritoneum, due to
 intra-abdominal generalized infection. With the exception of the primary ones which are the
 result of a bacterial translocation from the gastro-intestinal tract or an abdominal
 contamination for hematogenous way sometimes treatable with medical therapy alone,
 peritonitis represents a complex condition that requires an early surgical treatment.

 Mortality linked to the peritonitis is extremely high and variable between 42% and 80% when
 associated with a systemic framework of severe sepsis. This variability is linked to a number
 of risk factors, including advanced age of the patients, the presence of comorbidity, male
 sex, a poor nutritional status, and a number of re-operations; as well as specific
 characteristics related to the type of infection, the timing of surgery, the beginning of an
 appropriate and early antibiotic therapy.The post-operative treatment of the patient with
 peritonitis significantly affects the outcome of the same. The presence of peritonitis and
 then the seizure of large volumes of liquids and the possible state of systemic vasodilation
 induced by the infectious process, provide a framework of hypovolemia. There is a literature
 that identifies in abdominal trauma damage patient's volemic aggressive resuscitation an
 element of pejorative outcomes. The purpose of this work is to evaluate the clinical changes
 determined by a different volemic strategy.
DEPARTMENT OF GENERAL SURGERY AND SURGICAL SPECIALITIES SERVICE OF ANESTHESIOLOGY AND
 REANIMATION INTENSIVE CARE UNIT

 Head: Prof. M. Girardis

 MANAGEMENT OF THE PATIENT WITH ACUTE ABDOMEN SUBMITTED TO URGENT ABDOMINAL SURGERY: pilot
 study randomized multicentre

 INTRODUCTION Acute abdomen is the clinical manifestation of irritation of the peritoneum, due
 to intra-abdominal generalized infection. Mortality linked to the peritonitis is extremely
 high and variable between 42% and 80% when associated with a systemic framework of severe
 sepsis. This variability is linked to a number of risk factors, including advanced age of the
 patients, the presence of comorbidity, male sex, a poor nutritional status, and a number of
 reoperations; as well as specific characteristics related to the type of infection, the
 timing of surgery, the beginning of an appropriate and early antibiotic therapy.

 The post-operative treatment of the patient with peritonitis significantly affects the
 outcome of the same.

 The centers involved in the study will be three:

 1. post operative intensive care unit (ICU) - Modena University Hospital

 2. reanimation unit - Carpi Hospital

 3. intensive care unit (ICU) - Modena New Civil Hospital

 OBJECTIVES PRIMARY OBJECTIVES: differences between the two treatment groups with different
 fluidic strategy in terms of 30-day mortality.

 SECONDARY OBJECTIVES: differences between the two treatment groups with different fluidic
 strategy in terms of surgical complications, occurrence of organ failure, duration of
 mechanical ventilation and length of stay in ICU. Please refer to Section 6 for the
 definition of the endpoints / response variables for the secondary goals.

 PLAN STUDY Study setting

 The study will be conducted at the following facilities:

 1. post operative intensive care unit (ICU) at Modena University Hospital

 2. intensive care unit (ICU) at Modena Baggiovara

 3. reanimation unit at Carpi Inclusion criteria All patients with acute abdomen undergoing
 abdominal surgery under emergency and presenting on arrival in ICU at least a sign of
 bad perfusion.

 In the definition of acute abdomen, the following frameworks will be included:

 1. primary peritonitis: bacterial contamination of the peritoneal cavity by microorganisms
 starting from extra-peritoneal sites (hematogenous in sepsis / bacteremia, from the
 female genital tract in the course of pelvic inflammatory disease (PID), from the
 retroperitoneum); translocation of microorganisms through the bowel

 2. secondary peritonitis: bacterial contamination of the peritoneal cavity as a result of
 phlogosis or perforation of the digestive tract or female genital tract:

 1. acute abdominal infections (appendicitis, diverticulitis, cholecystitis,
 gallbladder empyema, suppurative cholangitis)

 2. other diseases (occlusion of the mesenteric, gastric or duodenal ulcer,
 strangulated hernia or volvulus, colic neoplasia, toxic megacolon, ruptured of
 intraperitoneal or visceral abscess)

 3. various intestinal diseases (tuberculosis, typhoid fever, cytomegalovirus (CMV)
 infection, infection with Clostridium)

 4. penetrating and not abdominal trauma (rupture or perforation of a hollow internal
 organ)

 5. surgical operation (stomach and duodenum, ileum, colon - rectum, bile - ducts) for
 dehiscence of anastomosis and / or sutures

 3. tertiary or relapsing peritonitis, understood as persistent or recurrent peritonitis
 after apparently adequate medical and surgical treatment of secondary peritonitis

 4. intestinal ischemia

 5. pancreatitis with or without evidence of hemorrhagic- necrotic areas

 The condition of hypoperfusion is identified by:

 1. perioperative metabolic acidosis that can not be explained by other morbid conditions

 2. arterial hypotension with PAM <60 mmHg or less than 15% of the preoperative

 Exclusion Criteria

 1. Patients with chronic renal failure already receiving dialysis treatment.

 2. Acute Coronary Syndrome (ACS) <12 months and New York Hearth Classification (NHYA )
 class > 3

 3. Patients judged at the admission not subject to resuscitative measures for severity and
 comorbidity

 4. Patients with massive hemorrhage in operative room or in the immediate perioperative
 with the need for blood transfusions and abundant blood products > 5 units of
 Erythrocyte Concentrates (EC)

 5. Patients scheduled for Orthotopic Liver Transplantation (OLT)

 6. Patients younger than 18 years old

 In the definition of ACS, chest pain of suspected coronary origin with or without ST-segment
 elevation are included. According to the classification accepted by the European Society of
 Cardiology (ESC) and by the American College of Cardiology (ACC), the serum dosage of cardiac
 troponins can make the diagnosis of myocardial infarction.

 STUDY PROCEDURES Screening and inclusion

 At the entrance to the ICU all patients that meet the criteria for inclusion and don't
 present exclusion criteria - will be evaluated for randomization.

 The attending physician will have to notify the coordinating center as soon deemed to have
 identified a patient to be enrolled. The coordinating center is at the Intensive Care Unit of
 the University Hospital of Modena.

 Randomization must be done at the time of admission to ICU.

 The method of randomization will be by "parallel group", the type of simple randomization and
 the randomization list will be obtained through the use of a random number generator
 computerized in a 1:1 ratio. Patients who meet the inclusion criteria are assigned over the
 telephone by medical coordinator:

 1. or to the group receiving volemic standard treatment (conventional)

 2. or to the group receiving volemic small treatment (restrictive) The contact number for
 randomization is always 0594224896

 Group "conventional"

 Goals of the treatment:

 1. arterial pressure mean ≥ 65 mmHg or equal to the pre-operative

 2. diuretic rhythm ≥ 1 ml / Kg / h

 3. venous saturation in vena cava ≥ 70% or mixed venous saturation as Swan Ganz's catheter
 (SG) ≥ 65%

 4. base excess (BE) > - 3

 5. Central Venous Pression (PVC) ≥ 8 mmHg; for patients undergoing mechanical ventilation,
 this limit may be raised to 12-15 mmHg.

 To achieve the therapeutic goals set out above will be executed a volemic fill until reaching
 central venous pressure values of 8-10 mmHg. Crystalloid solutions and specifically balanced
 III, Ringer solutions or alternatively glucose solution will be infused at 5% in patients
 with serum sodium ≥ 145 milliequivalent (mEq) / L.

 For this group of patients, the overall water balance won't be binding. If after proper
 filling the targets aren't yet achieved, the patient will begin infusion of vasoactive drugs
 following the practice of department.

 If you are unable to get a goal value of venous saturation you can consider:

 1. The chance to infuse additional volumes of fluids

 2. the chance to transfuse concentrate red blood cells

 3. The chance to infuse dobutamine up to 20 microg / kg / min

 Group "restrictive"

 Goals of the treatment:

 1. arterial pressure mean ≥ 60 mmHg or ≥ 10% less than the preoperative values

 2. diuretic rhythm ≥ 0.5 ml / kg / h

 3. venous saturation in vena cava ≥ 60% or mixed venous saturation ≥ 55% by SG

 4. BE> - 5

 5. PVC goal not necessary

 To achieve the therapeutic goals set out above will be executed a volemic fill up to values
 of PVC ≤ 5 mmHg or at maximum values of 2 mmHg more the incoming If after proper filling the
 targets aren't yet achieved, the patient will begin infusion of vasoactive drugs following
 the practice of department. If after 12 hours of admission the water balance will be > 10-15
 ml / kg / h an infusion of furosemide should be initiated in order to bring the budget of the
 patient to 10-15 ml / kg in 24 hours.

 DATA COLLECTION Data Collection Program

 Data collection will be done by compiling data collection forms. In particular, the following
 types of data collection formats will be filled:

 1. basal and randomization card (Record Form 1)

 2. card to 6 hours after randomization (Record Form 2)

 3. 24 hours card (Record Form 3)

 4. daily continuation card (as long as the patient is admitted to Post Operative Intensive
 Therapy, Record Form 4)

 5. Conclusion card (Record Form 5)

 The basal card will contain:

 1. patient's personal details

 2. information according with remote and proximal medical history

 3. patient's vital parameters

 4. patient's therapy

 The final board will collect data until it will be verified:

 1. patient's discharge from the hospital

 2. thirtieth day of hospitalization

 3. patient's death

 END POINT / VARIABLE RESPONSE

 Study end point:

 1. Primary: Mortality at 30 days

 2. Secondary:

 1. Number of surgical complications (anastomotic dehiscences, need for re-operation,
 need for percutaneous drainages of evacuation, the development of abdominal
 hypertension).

 2. Occurrence of acute respiratory failure identified with respiratory exchanges with
 values of P / F less than 300 mmHg

 3. Occurrence of lack of circulation with the use of vasoactive amines in the
 post-operative

 4. Occurrence of acute renal failure (number of extracorporeal treatments and / or
 serum creatinine ≥ 1.9 mg / dl)

 5. Occurrence of hepatic insufficiency with serum total bilirubin values greater than
 2.0 mg / dl

 6. Days of mechanical ventilation

 7. Days of ICU staying

 In the definition of surgical complications all the following situations are included:

 1. anastomotic dehiscences

 2. the need for reoperation

 3. the need to place percutaneous drainages of evacuation

 4. wound infection that requires surgical toilet or with microbiological samples positive

 The accepted definition of abdominal hypertension is hypertension of the abdominal cavity of
 retroperitoneal, intraperitoneal or parietal origin. The measurement system accepted in the
 study is exclusively that one of the intravesical bladder catheterization. The values
 considered as reference are:

 1. mild abdominal hypertension: 10-20 mmHg

 2. moderate abdominal hypertension: 20-40 mmHg

 3. severe abdominal hypertension: > 40 mmHg The numeric variables which indicate organ
 failure shall be guided by the SOFA score for severity score ≥ 2. In extracorporeal
 treatments hemo-filtration sessions with both intermittent and continuous methods are
 considered.

 SIZE OF THE STUDY AND DATA ANALYSIS CRITERIA This is a phase II study, which is exploratory
 and estimative and that involves randomization of all recruitable patients during the period
 of study all over the three centers involved in the work. The study will begin on January
 2010 and will last for 3 years. The sample size has been calculated on the basis of the
 available data at the Post-Operative Intensive Care Unit of the Hospital in 2007: these data
 showed a mortality of the patients with acute abdomen undergoing abdominal surgery under
 emergency and presenting at the moment of arrival to Post Operative Intensive Therapy at
 least a sign of hypoperfusion of 30%. Assuming a two-tailed alpha level <0.05 and a power of
 80%, we have calculated that 100 patients per arm are needed to detect an absolute reduction
 in mortality of 15%. This reduction appears to be significant from the clinical point of view
 considering previous trials of fluidic therapy in shocked patients . For comparisons between
 the means, the t-student test will be used. For comparison of events frequencies the χ2 test
 or Fisher's test - as indicated - will be used. A p <0.05 will be considered statistically
 significant. Static analysis will be performed using version 16.0 of SPSS software.
Inclusion Criteria:

 All patients with acute abdomen undergoing abdominal surgery under emergency and presenting
 on arrival in ICU at least a sign of bad perfusion.

 Exclusion Criteria:

 1. Patients with chronic renal failure already receiving dialysis treatment

 2. Acute Coronary Syndrome (ACS) <12 months and New York Hearth Classification (NHYA )
 class > 3

 3. Patients judged at the admission not subject to resuscitative measures for severity
 and comorbidity

 4. Patients with massive hemorrhage in operative room or in the immediate perioperative
 with the need for blood transfusions and abundant blood products > 5 units of
 Erytrocyte Concentrates (EC)

 5. Patients scheduled for Orthotopic Liver Transplantation (OLT)

 6. Patients younger than 18 years old