Hypertonic Saline Versus Isotonic Saline in Septic Shock (Effects on Morbidity, Mortality, and Clinical Outcome)

1 Introduction

Sepsis and the systemic inflammatory response syndrome (SIRS) are common and represent a major factor in morbidity and mortality in intensive care units (ICUs) and the critically ill. The pathogenesis of these syndromes is becoming increasingly understood and it is hoped that this will result in improved outcome.1

SIRS is the clinical response to infection manifested by two or more of the following criteria.

Temperature >38°C or <36°C. HR > 90bpm. Respiration >20 breaths/min. WBC count >12,000/mL or <4000 mL or >10% immature neutrophils.

Sepsis is defined as confirmed or clinically suspected infection plus 2 or more SIRS criteria.

Sever sepsis defined as sepsis and one or more organ dysfunction, while septic shock is defined as sepsis plus hypotension (… 90 mm Hg) despite fluid resuscitation.1

As proved infusion of several liters of isotonic fluids is associated with the adverse effects of extravasation into the interstitial space. In sepsis, in particular, this may result in peripheral and/or pulmonary edema.2

A large number of very interesting experiments highlighted that hypertonic saline resuscitation may decrease susceptibility to post-traumatic sepsis, trauma and sepsis-induced immune dysfunction, inflammatory, inflammatory response and apo- ptosis.3

2 Aim of the work

This study is designed to compare the effects of hypertonic saline/ hydroxyl-ethyl starch (HSS/HES) and isotonic saline/hydroxyl- ethyl starch (ISS/HES) on hemodynamic, inflammatory mediators, and clinical outcome in septic shock.

3 Patients and methods

All consecutive critically ill patients admitted to critical care department in Ahmed Maher Teaching Hospital. Were screened for patients with the diagnosis of septic shock. 40 patients were eligible when they met the inclusion criteria for septic shock, the 40 patients divided to 2 groups: the first group received isotonic saline 0.9% and HES while the second group received 2 boluses of hypertonic saline 3% (4 mL/kg at a rate 1 mL/kg/min) in addition to ISS and HES.

Hypertonic solutions may be able to resuscitate critically ill patients with septic shock better and more rapidly, than crystalloid infusion (eg, 0.9% sodium chloride or lactated Ringer's solution).

Septic shock. It denotes sepsis-induced hypotension not corrected by fluid loading and needs inotropic and/or vasopressor support. Perfusion abnormalities too many organs characterize the shock state.1

Patients who were diagnosed as having septic shock at ICU admission and did not meet any of the exclusion criteria were selected randomly and prospectively included into the study on the day of ICU admission either coming from the emergency room or already hospitalized.

3.1 Exclusion criteria 1. Trauma patients 2. Burn patients 3. Patients < 18 years 3.2 Inclusion criteria 1- Age > 18 years 2- Septic shocka. Clinically suspected infection (or confirmed) infection anywhere. b. Two or more of the following: temperature >38°C (100.4°F) or <36°C (96.8°F), heart rate (HR) > 90/min, respiratory rate (RR) > 20/min or PaCo2 < 32 mm Hg, white blood cell count > 12.000/mm3 or <4.000/mm3 or >10% immature neutrophils. 3.3 Study design

Included patients with sepsis were subjected to the following:

1. Full clinical evaluation Including history and physical examination with special emphasis on vital signs blood pressure (BP), HR, temperature and RR, and Glasgow coma scale (GCS), which were evaluated at the day of admission and daily thereafter. 2. Laboratory investigations Routine labs: - Complete blood count: hemoglobin (PT), hematocrit, white blood cells, and platelet count. - Coagulation profile: prothrombin time, prothrombin concentration, and international normalizing ratio (INR) - Arterial blood gases (ABGs). - Liver Function Tests: alanine amino-transferase, aspartate amino-transferase, bilirubin and albumin. Kidney function Test: Na, K, urea, and creatinine. This routine labs were done on admission and subsequently there-after every day until ICU discharge or demise to a total of 7 days. Labs specific for the study: C-reactive protein in day 0, 1, 2, 7. By enzyme linked immune-sorbent assay 3. Micro-biological studies: Including Pan-cultures (sputum, blood, urine, or biological fluid according to clinical suspicion) prior to antibiotic administration or after discontinuation of antibiotic for 48 hours. 4. Imaging studies: identify the source of sepsis (eg, abdominal ultrasound and chest x-ray), Echo-heart measuring cardiac output (CO), ejection fraction, and fractional shortening) in days 0, 1, 2, and 7 5. Clinical data: These data were evaluated up to a maximum follow period of 7 days. - Length of ICU stay. - Need for and duration of mechanical ventilation. - Need for and duration of inotropic support. - Need for renal supportive therapy (hemo-dialysis) - Final outcome: Eventually patients were sub-grouped into survivors and non-survivors within 1 week follow up then compared all studied variables. 6. Application of acute physiology and chronic healthy evaluation II (APACHE II), sequential organ failure assessment (SOFA) and multiple organ damage scores (MODs): APACHE II score evaluated on admission while SOFA and MOD scores were evaluated serially every day until ICU discharge or demise or up to a total of 7 days. 1. APACHE II: After admission of a patient to ICU, an integral score based on several measurements; higher scores imply a more severe disease and a higher risk of death. 2. SOFA score: The SOFA score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based in 6 different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. 3. MOD score: The MOD score is a scoring of system to determine the extent of organ function or rate of failure. 3.4 The statistical methods

Data were statistically described in terms of range, mean ± standard deviation (±SD), median, frequencies (number of cases) and relative frequencies (percentages) when appropriate. Comparison of quantitative variables between the study groups was done using Mann-Whitney U test for independent samples. For comparing categorical data, chi-square (c2) test was performed. Fisher exact test was used when the expected frequency is <5. Receiver operator characteristic analysis was used to determine the optimum cut off value for the studied diagnostic markers. Correlation between various variables was done using Pearson correlation coefficient for continuous variables.

A probability value (P) < .05 was considered statistically significant. All statistical calculation were done using computer programs Microsoft Excel 2010 (Microsoft Corporation, New York, NY) and Statistical Package for the Social Science (version 17, SPSS Inc., Chicago, IL) for Microsoft Windows.

4 Results

Our study was done in Ahmed Maher teaching hospital and was designed as prospective study that enrolled forty patients admitted to our ICU suffering from septic shock who were divided into two groups:

Group I: 20 pts who received routine resuscitation fluids.

Group II: 20 pts who were received 2 boluses of 3% hypertonic saline in addition to routine resuscitation fluids.

Comparing the age of the 2 groups there was insignificant difference between them as shown in Table 1 (57.6 ± 20.7 years in group 1 versus 51.6 ± 12.5 years, P: .27).

Table 1 - Age in groups I and II Age Mean N SD P Group I 57.65 20 20.76 .27 Group II 51.65 20 12.59

As regard gender both group showed similar ratio for femalemale percentage. Comparing the two groups for existence of co. morbid conditions showed no significant difference between them (Table 2).

Table 2 - Co-morbid conditions Group I Group II N % N % P Smoker 4 20 7 35 .48 Steroid 3 15 2 10 1 DM 10 50 10 50 1 HTN 5 25 7 35 .7 Cardiac 5 25 3 15 .69 COPD 4 20 4 20 1 CNS disorders 4 20 3 15 1 Renal 6 30 3 15 .45 Hepatic 4 20 5 25 1
4.1 Glasgow coma scale

GCS was matched without significant difference between the two groups on admission and then showed transient improvement on 2nd, 3rd, and 4th days in group II then showed in-significant difference by last follow up as shown in Figure 1.

Figure 1:

Comparing group I and II as regard (GCS) for 7 days.

4.2 Mean arterial blood pressure

Regarding mean arterial blood pressure (MABP) was matched on admission for both group and showed transient nonpersistent improvement in group II at day 2 and day 3 as shown in Figure 2.

Figure 2:

MABP in both groups compared for 7 days.

4.3 Heart rate

The HR was not significantly different between the two groups on admission but HR tended to improve and became significantly lower in group II by 4th, 5th, and 6th days than group I shown in Figure 3.

Figure 3:

Heart rate in Group I vs Group II.

As regards body temperature Respiratory rate central venous pressure (CVP), and urine output (UO), there was insignificant difference between the two groups throughout their ICU stay.

4.4 Echocardiographic parameters

Cardiac output tended to improve significantly in group II on day 1 and 2 as shown in Table 3.

Table 3 - Cardiac output in HTS vs ISS Group I Group II Mean ± SD N Mean ± SD N P Day 0 5.53 ± 1.61 20 5.87 ± 1.29 20 .296 Day 1 5.31 ± 1.10 20 5.95 ± 0.83 20 .042 Day 2 4.65 ± 1.21 20 5.74 ± 0.87 19 .003 Day 7 4.91 ± 1.26 8 4.90 ± 0.37 6 .982