Perfusion Index Derived from Pulse Oximetry, Serum actate, its Surrogates and Beta Type Natriuretic Peptide (Bnp) for Outcome Prediction in Poly-Traumatized Patients. A Prospective Observational Cohort Study

Key messages

• Lactate clearance is a useful prognostic factor of mortality in adult poly-traumatized patients with blunt trauma; AUC 0.96.
• The Perfusion index is a useful prognostic factor of mortality in adult poly-traumatized patients with blunt trauma; AUC 0.93.
• Serum lactate is a weak prognostic factor of mortality in adult poly-traumatized patients with blunt trauma; AUC 0.57.
• The beta Natriuretic peptide has no prognostic value of mortality in adult poly-traumatized patients with blunt trauma; AUC less than 0.5. Abbreviations: APACHE: Acute Physiology and Chronic Health Evaluation; ARF: Acute Renal Failure; ATLS: Advanced Trauma Life Support; AUC: Area Under the Curve; BD: Base Deficit; BNP: Beta Type Natriuretic Peptides; CO: Centigrade; CO2: Carbon Dioxide; CVP: Central Venous Pressure; DIC: Disseminated Intravascular Coagulopathy; EIA: Enzyme Immune Assay; ICU: Intensive Care Unit; IV: Intravenous; MAP: Mean Arterial Pressure; Mmol/l: Millimole Per Litre; NE: Nor Epinephrine; NT pro BNP: N-Terminal Pro Beta Natriuretic Peptide; OCT: Oxygen Challenge Test; PaCO2: Arterial Pressure Of Carbon Dioxide; PaO2: Arterial Partial Pressure Of Oxygen; PI: Peripheral Perfusion Index; PtcCO2: Transcutaneous Partial Pressure Of Carbon Dioxide; PtcO2: Transcutaneous Partial Pressure Of Oxygen; Pv-aCO2: Difference Between Central Venous And Arterial PCO2; RBCs: Red Blood Cells; ROC: Receiver Operating Characteristic; RTS: Revised Trauma Score; ScvO2: Central Venous Oxygen Saturation; SOFA: Sequential Organ Failure Assessment; SPSS: Statistical Package for the Social Sciences

Introduction

Major injury with severe hemorrhagic shock can progress to organ hypo-perfusion, failure and even death. Decreased perfusion because of intra-vascular volume depletion and hindered oxygen delivery results in regional hypoxia and anaerobic metabolism. The peripheral circulation first to suffer and last to regain blood flow during resuscitation; used as a target for monitoring compared to other prognostic markers of anaerobic metabolism as lactate and its surrogates. Even beta Natriuretic peptide (BNP) can predict the outcome of patients with major injuries [1]. Perfusion index (PI) is a non-invasive numeric value of peripheral perfusion; gained from pulse oximetery. Perfusion index is the ratio Alaa M Atia, et al. Perfusion Index Derived from Pulse Oximetry, Serum Lactate, its Surrogates and Beta Type Natriuretic Peptide (Bnp) for Outcome Prediction in Poly-Traumatized Patients. A Prospective Observational Cohort Study Anaesth Critic Care Med J 2016, 1(1): 000102.

of the pulsatile blood flow to the non-pulsatile static blood flow in patient’s peripheral tissue (pulsatile component / non-pulsatile component of the plethysmographic waveform × 100%) and is now displayed on some pulse Oximeters. In universal terms, PI reflects peripheral vasomotor tone. Low PI suggests peripheral vasoconstriction or severe hypovolaemia and high PI suggests vaso-dilatation. The PI’s value ranges from 0.2% for weak pulse to 20% for a strong pulse [2] It has been reported that perfusion index traced from pulse Oximeters can monitor peripheral perfusion in critically ill patients [3]. Recently, Huai-Wu and others, in a prospective observational study compared perfusion index to trans-cutaneous oxygen saturation/ carbon dioxide tension (ptcO2/ptcCO2), oxygen challenge test (OCT) in a group of septic patients. Perfusion index found similar to arterial lactate to predict mortality [4]. The value of non-invasive monitoring of peripheral perfusion to predict outcome remains to be explored in poly- traumatized patients. To the best of our knowledge, no study has addressed the sensitivity of perfusion index compared to lactate, its surrogates and serum beta Natriuretic peptide (BNP) to predict mortality in such critical poly-traumatized patients in a prospective study.

Results

The study included 50 adults poly-traumatized patients with blunt trauma; fulfilling the inclusion criteria (43 men and 7 women), with a mean age (27.5± 8.0 years), of whom 36 survived (72%) and 14 non-survivors (28%) (Figure 2). The admission Revised Trauma Score (5.9236±0.3996) and the admission SOFA score (6.7±1.31), the final SOFA score (6.5±3.75). All over the 48-hour study period; patients received crystalloid volume (5700±2130.9 ml), colloid volume (1710±1030.6 Copyright© Alaa M Atia, et al.

ml), packed RBCs (4.6±1.6 units), fresh frozen plasma (3.42±2.5 units) and nor adrenaline doses (0.312±0.431 ug/kg/minute). Peripheral perfusion parameters include admission perfusion index (0.2±0.06). Hemodynamic parameters on admission showed a mean heart rate (149.3±6.1 beat/min), systolic blood pressure (60.12±11.08 mmHg), diastolic blood pressure (29.22±7.81 mmHg), mean blood pressure (39.52±8.21 mmHg) and central venous pressure (-3.98±1.64 cmH2o).

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Figure 2: mortality and cause of death.

• DIC: Disseminated intravascular coagulopathy
• ARF: Acute renal failure Metabolic perfusion parameters showed a mean baseline serum lactate (6.9±1.7 mmol/L), mean base deficit (-20.3±2.8 mmol/L). The comparison between survival group and non-survival group about demographic data, revised trauma score (RTS), SOFA score, nor adrenaline dose and resuscitation by blood products and fluids. Age, sex, packed RBCs and fresh frozen plasma transfusion showed nonsignificant difference between survival and non-survival group. However, RTS, SOFA-0, SOFA-f, noradrenaline dose, The crystalloid and colloid volume used showed a statistically significant difference between survival and non-survival group (P< 0.05) and have significant correlation with mortality. Revised Trauma Score is a reliable predictor of mortality and had significant correlation with mortality (P< 0.001). Non- survivors had significantly lower RTS than survivors (P< 0.001). However, SOFA-0 and SOFA-f had significant correlation with mortality. Non-survivors had Alaa M Atia, et al. Perfusion Index Derived from Pulse Oximetry, Serum Lactate, its Surrogates and Beta Type Natriuretic Peptide (Bnp) for Outcome Prediction in Poly-Traumatized Patients. A Prospective Observational Cohort Study Anaesth Critic Care Med J 2016, 1(1): 000102.

significantly higher SOFA-0 and SOFA-f than survivors (P< 0.001). A significant correlation between nor adrenaline dose and mortality (P< 0.001) found. Nor adrenaline dose significantly higher in non-survivors (P< 0.001). Crystalloid and Colloid volume significantly correlated with mortality (P< 0.001) and significantly higher in non- survivors than survivors (P< 0.001). However, transfusion products (packed RBCs and fresh frozen plasma) had a statistically non significant correlation with mortality (P> 0.05).

Perfusion index changed significantly from baseline (PI- 0) (p< 0.001) in survivors and non-survivors. Perfusion index showed a non significant difference between survivors and non-survivors in the first six hours, post resuscitation. After the first 6 hours, post resuscitation; perfusion index showed a statistically significant difference between survivors and non-survivors (P< 0.01). Non-survivors had significantly lower PI than survivors (p< 0.001) (Figure 3).

Perfusion index changes in survivors and non survivors $$ \mathrm {E} = \frac {1}{2} \mathrm {A} ^ {2} + \mathrm {B} ^ {2} $$ $$ \diamond $$ $$ \mathrm {E} = \frac {1}{2} \mathrm {A} ^ {2} + \mathrm {B} ^ {2} $$ $$ \diamond $$ $$ \mathrm {E} = \mathrm {E} _ {1} + \mathrm {E} _ {2} + \dots + \mathrm {E} _ {n} $$ $$ \Delta $$ $$ \mathrm {E} = \frac {1}{2} \mathrm {A} ^ {2} + \mathrm {B} ^ {2} $$ $$ \Delta $$ $$ \mathrm {E} = \frac {1}{2} \mathrm {A} ^ {2} + \mathrm {B} ^ {2} $$ $$ \diamond $$ $$ \mathrm {E} = \frac {1}{2} \mathrm {A} ^ {2} + \mathrm {B} ^ {2} $$ $$ \Delta $$ $$ \diamond $$ $$ \mathrm {E} = \frac {1}{2} \mathrm {A} ^ {2} + \mathrm {B} ^ {2} $$ $$ \diamond $$ $$ \square $$ $$ \mathrm {E} = \mathrm {E} _ {1} + \mathrm {E} _ {2} + \dots + \mathrm {E} _ {n} $$ $$ \mathrm {E} = \frac {1}{2} \mathrm {A} ^ {2} + \mathrm {B} ^ {2} $$ $$ \square $$ $$ \square $$ $$ \mathrm {E} = \mathrm {E} _ {1} + \mathrm {E} _ {2} + \dots + \mathrm {E} _ {n} $$ $$ \square $$ $$ \mathrm {E} = \frac {1}{2} \mathrm {A} ^ {2} + \mathrm {B} ^ {2} $$ $$ \diamond $$ $$ \mathrm {E} = \mathrm {E} _ {1} + \mathrm {E} _ {2} + \dots + \mathrm {E} _ {n} $$ $$ \square $$ $$ \mathrm {E} = \frac {1}{2} \mathrm {A} ^ {2} + \mathrm {B} ^ {2} $$ $$ \square $$ $$ \mathrm {E} = \mathrm {E} _ {1} + \mathrm {E} _ {2} + \dots + \mathrm {E} _ {n} $$ $$ \mathrm {E} = \frac {1}{2} \mathrm {A} ^ {2} + \mathrm {B} ^ {2} $$ $$ \square $$ $$ \square $$ $$ \mathrm {E} = \mathrm {E} _ {1} + \mathrm {E} _ {2} + \dots + \mathrm {E} _ {n} $$ $$ \mathrm {E} = \mathrm {E} _ {1} + \mathrm {E} _ {2} + \dots + \mathrm {E} _ {n} $$ $$ \mathrm {E} = \mathrm {E} _ {1} + \mathrm {E} _ {2} + \dots + \mathrm {E} _ {n} $$ $$ \diamond $$ $$ \square $$ $$ \square $$ Figure 3: Perfusion index changes in survivors and non survivors. ROC curve analysis of perfusion index at 24 hours, post resuscitation; showed the ideal cutoff point for predicting mortality ≤ 0.75 with AUC 0.93, sensitivity 97% and specificity 82% (Figure 4).

Copyright© Alaa M Atia, et al.

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Discussion

The value of routine blood pressure and pulse rate monitoring in patients with hemorrhagic shock as markers of tissue perfusion became questionable. Other monitoring tools have been recently introduced; among them, monitoring of peripheral perfusion during the resuscitation and post resuscitation stages of shock. Peripheral perfusion can be gravely compromised during shock which has been correlated with cardiac output, hyperlactatemia, and organ dysfunction [9]. Many reports showed that traditional vital signs alone are not reliable measures of acute hemorrhage due to compensatory mechanisms. [10, 11, 12] Hernandez and others mentioned that, notwithstanding, no work has assessed the temporal profile of changes in peripheral perfusion during severe shock and resuscitation or has compared the kinetics of development of peripheral perfusion versus traditional metabolic perfusion parameters. This will offer valuable insights about perfusion monitoring in the critically ill patients and help to describe the potential role and limitations of peripheral perfusion as a target for resuscitation [13]. This prospective observational study showed that perfusion index was low on admission, which could be a valuable tool in diagnosing the severity of bleeding, monitoring resuscitation and predicting mortality. Perfusion index showed a statistical significant difference between survivors and non-survivors after 6 hours, post resuscitation. ROC analysis showed the ideal PI cutoff point for predicting mortality ≤ 0.75 with AUC 0.93, sensitivity 97% and specificity 82%. Examining the correlation between perfusion index and serum lactate on admission showed a statistically nonsignificant correlation, but showed a statistically significant inverse correlation at all times after resuscitation. Smetkin and others found PI < 1 is accompanied by other signs of hypo-perfusion in a group of critically ill patients as confirmed by increased lactate and increased Copyright© Alaa M Atia, et al.

venous-end tidal CO2 difference. So, the PI may be used for non-invasive assessment of peripheral blood flow in critical conditions. They determined that in patients who had “decreased” perfusion PI < 1, there was a tendency to inverse correlation between PI and lactate and patients with “normal” perfusion had lower blood lactate than the “decreased” perfusion group [14]. Recently; Huai-Wu and others found PI and Oxygen Challenge Test are predictive of mortality in septic shock patients after resuscitation. They reported the control group had a higher baseline PI than the septic shock group. In the sepsis group, the macro hemodynamic parameters and ScvO2 showed no differences between survivors and non-survivors. The non-survivors had significantly lower PI and higher arterial lactate levels. The PI predicted the ICU mortality with accuracy similar to arterial lactate level. A PI < 0.2 related to poor outcome after resuscitation with area under ROC curve 0.84, sensitivity 55% and specificity 73% [4]. Lima and others proposed a standardized quantitative clinical assessment of peripheral perfusion. An abnormal peripheral perfusion as explained by this approach associated with hyperlactatemia and predicted a worsening SOFA score at 48 hours [15]. In this study, serum lactate was a weak predictor of mortality. Non-survivors had a higher serum lactate level. A cutoff point as traced from the ROC analysis showed a lactate level >2.25 mmol/L in non- survivors (AUC 0.57). A statistically significant positive correlation between lactate and mortality has been also shown. In trauma patients with blood lactate level relative to their vital signs, mortality rate of 28% for patients with mean first lactate (8.33±2.59 mmol/L) or more suggests a high hazard of mortality which could be immediately on arrival to the emergency section. One study found that a cutoff value of 4 mmol/L has a prognostic significance in the emergency department [16]. Compared with our results; recently, a point of care testing depends on venous sample proved comparable to arterial measurement with good correlation in trauma patients. Jansen and others studied capillary or venous lactate levels using a handheld device on arrival at the scene and just before or on arrival at the emergency department. The main outcome tested was in-hospital mortality. They settled that non-survivors had significantly higher lactate levels than survivors. Mortality was significantly higher in patients with lactate levels of 3.5 mmol/L or higher compared with those with lactate levels below 3.5 mmol/L. Likewise, without hypotension, mortality was higher in those with higher lactate levels. Pre-hospital blood lactate levels associated with in- Alaa M Atia, et al. Perfusion Index Derived from Pulse Oximetry, Serum Lactate, its Surrogates and Beta Type Natriuretic Peptide (Bnp) for Outcome Prediction in Poly-Traumatized Patients. A Prospective Observational Cohort Study Anaesth Critic Care Med J 2016, 1(1): 000102.

hospital mortality and provided prognostic information superior to that supplied by the patient's vital signs [17]. Lactate clearance within 48 hours and survival in trauma patients also reported by pal and others in a large scaled study with 5995 trauma patients, comparing the admission lactate value to mortality. They settled that admission serum lactate levels do not predict mortality in the acutely injured patients [18]. MC Nelis and others, in a study of 96 patients reported that mortality significantly increased when lactate clearance is prolonged [19]. In our study, the mortality of patients did not clear lactate within 48 hours post resuscitation was 28%. This is similar to previously reported studies with mortality rate 14-33% [19, 20]. The early assessment of hypovolemic shock, predicting transfusion need and mortality in multi-injured patients are still among the most challenging tasks in the early management of multi-injured patients. In our study, base deficit showed a statistically significant difference between survivors and non- survivors (P< 0.01). Base deficit was significantly higher in non-survivors. ROC analysis showed the ideal base deficit cutoff point for predicting mortality > (-8.0) mmol/L with AUC 0.90. Multiple studies showed that ATLS classification system may not accurately show the degree of hemorrhage in poly-traumatized patients. This system overestimates the degree of tachycardia to hypotension and underestimates mental status. In addition, individual items of the system are poor predictors of bleeding. This contributed to re-interest in base deficit as a predictor of morbidity and mortality. A base deficit oriented classification of hemorrhagic shock has developed. Mutschler and others created a classification system based on base deficit in patients with blunt trauma. Whether this system applies to penetrating injuries is still questionable [21]. Martin and others reviewed all intensive care unit patients with simultaneously got lactate and base deficit measurements. The ability to predict mortality compared alone and in combination. Non-survivors had higher admission lactate and base deficit levels than survivors (both P<0.01), with a modest correlation (r =0. 52) between the measures. The admission lactate and base deficit levels had a similar prediction of mortality with areas under the ROC of 0.7 and 0.66, respectively (both P <0.01). There was no improvement in predictive ability using a combination of the 2 measures [22].

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It is to be stated that all these markers (perfusion index, serum lactate, lactate clearance and base deficit) cannot be used at the point of admission to provide the prognostic information about trauma mortality but they might be clinically relevant during the continuing resuscitation. BNP proved to be a prognostic marker in cardiac disease and sepsis [23]. However the prognostic value of BNP in trauma patients remains unclear. The present study displayed elevation of admission serum BNP in all poly-traumatized patients; still high levels got in non-survivors than survivors after 48 hours post trauma. ROC curve analysis showed low sensitivity and specificity of BNP to predict the outcome. The cause of high BNP in trauma patients remains unclear. It may be due to excessive volume resuscitation as described as a marker of fluid overload in transfusion and burn patients [24]. Friese and others reported a higher BNP with resuscitation after injury and levels were higher in patients developed pulmonary edema [25]. Bouras and others settled that no statistically significant difference in BNP levels observed among previously healthy multi- trauma patients (APACHE II score 2-8) with hemorrhagic shock (class II - III) and without head injury. This may show that current IV fluid therapy, at this stage of hemorrhagic shock may be inadequate and further investigation is needed [26]. Our study showed elevated BNP levels in poly-trauma patients without a prognostic value to predict outcome. This study explains for the first time that perfusion index is a sensitive monitor for the diagnosis of the severity of hemorrhagic shock, monitoring resuscitation and a useful prognostic factor of mortality in adult poly- traumatized patients with blunt trauma compared with metabolic parameters. Lactate clearance is a useful prognostic factor and serum lactate is a weak prognostic factor of mortality. BNP has no prognostic value of mortality in this study. Limitations of the survey were the modest number of patients admitted in the study with a short study period which may necessitate a further larger study. As BNP study of this work limited to admission and 48 hours, post resuscitation, it has a limited value in predicting outcome. Serial determinations in further works can be more informative in predicting outcome with BNP in adult poly-traumatized patients with blunt injury.

Alaa M Atia, et al. Perfusion Index Derived from Pulse Oximetry, Serum Lactate, its Surrogates and Beta Type Natriuretic Peptide (Bnp) for Outcome Prediction in Poly-Traumatized Patients. A Prospective Observational Cohort Study Anaesth Critic Care Med J 2016, 1(1): 000102.

Acknowledgments

The authors thank all nurses, residents, and other personnel of the trauma emergency department and the trauma intensive Care for their generous cooperation.