Comparison Of The Effects Of Norepinephrine And Phenylephrine On Tissue Oxygenation During An SVV Goal Directed Therapy In Elderly

Purpose: Fluid and volume management is the cornerstone for resuscitation of critically ill patients.Increasing evidence suggests that fluid management has great influence on patient’s outcome and overall morbidity and mortality.However,it has always been a tricky issue for anesthesiologists and clinicians especially in the setting of elderly patients.”the exact amount” of fluid to be infused remains a question.Over the past few years,two approaches in perioperative volume management were applied: Liberal and Restricted.Both techniques seem to cause postoperative complications.A restricted fluid therapy seems to induce tissue hypo perfusion,systemic inflammatory response syndrome,sepsis and multiple organ failure.Overzealous fluid resuscitation on the other hand is associated with edema,ileus,postoperative nausea and vomiting,pulmonary complications,compromised patient outcome and overall increased ICU and hospital stay.Both fluid overload and restriction seem to be harmful to patients and to their recovery.Multiple studies1,2,3,comparing these two strategies “Restricted VS Liberal” were conducted in different settings.The majority found that restrictive fluid therapy was superior to liberal since it decreased postoperative complications and overall ICU and Hospital stay.Recently,individualized goal-directed therapy became very appealing to clinicians since it achieves hemodynamic stability during and after surgery by optimizing cardiac preload,afterload,and contractility in order to accomplish a balance between systemic oxygen delivery and oxygen demand,therefore a better microcirculatory perfusion and tissue oxygenation.Goal directed fluid therapy was defined by Rivers et al.4as any hemodynamic optimization strategy in the perioperative setting utilizing parameters related to cardiac output and oxygendelivery in addition to classical parameters such as blood pressure and heart rate,avoiding either fluid overload or hypo perfusion and the complications related to both.As the population worldwide is aging,617 million people over 65 years old 4,the percentage of elderly presenting for surgery is exponentially growing as well,which increases fluid resuscitation problems encountered by clinicians.Old patients are known for their vulnerability to situations of stress due to the loss of functional reserve,fluid and electrolyte disorders,as well as physiological changes and comorbidities.All of these conditions in addition to the long fasting period,bowel preparation,surgical trauma and stress will increase the likelihood of dehydration and thus perioperative hypotension.Stroke volume variation(SVV)is an accurate,easy to use parameter that has high sensitivity and specificity in determining whether a patient is fluid responsive or not(by increasing stroke volume(SV)of10-15% after a fluid challenge)using Flo Trac?/Vigileo? system.Unlike static cardiac filling pressures used before such as central venous pressure(CVP),SVV showed promise results in guiding fluid therapy especially in critically ill and septic patients.Elderly can be prone to dehydration,thus to perioperative hypotension especially after induction of anesthesia,which makes the administration of vasopressors an imperative act to correct hypotension.In our study two vasopressors were used : Norepinephrine(NE)and Phenylephrine(PE).Norepinephrine was more talked about in literature and preferred by clinicians as it was proved to effectively increase tissue oxygenation and reduce the incidence of post-operative complications.Phenylephrine on the other hand,was less talked about in literature but was described as a potent vasoconstrictor with beneficial effects especially if administered in the form of infusion since the reflex bradycardia would be diminished.Nevertheless,Goal directed therapy seems to be the best approach until now,to guide individualized fluid replacement based on each patient’s cardiac response and stroke volume variation.However,no study has ever been conducted comparing phenylephrine and norepinephrine in the context of perioperative hypotension during GDT for elderly undergoing colon cancer surgery.The aim of our study is to compare the effects of both vasopressors on tissue oxygenation and perfusion in elderly over 65 years old after a bowel preparation.Methods : Data from 40 patients aged over 65 years old,who were American Society of Anesthesiologists(ASA)II or III and who underwent radical resection of colorectal carcinoma surgery were collected.Patients were randomly divided into two groups: Norepinephrine group(NE Group;n=20;5 μg/ml)and Phenylephrine group(PE Group;n=20;100 μg/ml).Both groups received an intraoperative basal fluid replacement of 5 ml/kg/h of crystalloid solution(Ringer’s acetate).An additional bolus of 200 ml colloid solution(Voluven 130/0.4;6%)was given when the SVV(measured by the Flo Trac / Vigileo 3.0)increased > 13 %.Fluid boluses were repeated every 5 min if the criteria were met until SVV <9%.In case SVV was between 9 and 13%,an infusion of 8ml /kg /h of crystalloid solution(Ringer’s acetate)was administered.In the case where SVV was more than 9% but less than13%,an infusion of crystalloid solution(Ringer’s acetate)at a rate of 5ml / kg/ h was started.The infusion of vasopressors(either norepinephrine or phenylephrine)started right after induction of anesthesia at a rate of 5ml/h in order to maintain a systolic arterial pressure > 90 mm Hg or MAP > 65 mm Hg and to correct induction hypotension usually occurring in elderly.In case blood pressure dropped to more than 20% of the baseline value and CI < 2.5 L/min/m2,a Dobutamine infusion was started.Central venous catheter was inserted via the right internal jugular vein and an arterial line was inserted into the radial artery of the non-dominant forearm.Standard monitoring including ECG,MAP,CVP,Sp O2,temperature,end-tidal carbon dioxide(ETCO2),and the bispectral index(BIS)were connected to the patient.In both groups,standard general anesthesia was induced with Etomidate,Fentanyl and Cisatracurium.A Flo Trac?/Vigileo? system was connected to the arterial line and hemodynamic parameters: HR,Sp O2,CVP,BP,SVV,SV,CI,CO,UO,BIS,T,ETCO2,ABG,VBG,CRT;were recorded on the following operating times: when arterial line is inserted,at induction time,3min after intubation,incision time and at the end of surgery.Result: We found that HR and MAP decreased in both groups towards the end of surgery while CVP increased,with a lower HR in phenylephrine group 65.45±10.25 compared to 69.4 ± 10.9 in norepinephrine group(p=0.751).SV,CI and COvalues increased at the end of surgery and were significantly lower in phenylephrine group.VBG and ABG correlated well except for Pa O2 values since arterial PO2 is280.36? mm? Hg greater than the venous in group 1 and 309.9mm Hg in group 2with significant variability.Lactate values were similar for both groups and no significant difference was observed.The volume of infused intraoperative crystalloid was lower(1682.5 ± 837)in the second group compared to the norepinephrine group(2143.5 ± 1014,p = 0.125).Similarly,the total infused volume of colloid in the second group was slightly lower(488.5 ± 153 compared to713 ± 529;p = 0.082).The total amount of infused vasopressors was lower in the phenylephrine group compared to norepinephrine(18.87 ± 20.68 ml VS 38.35 ±40.9 ml).The volume of blood loss,duration of anesthesia and CRT values,did not differ between the groups.Although both agents are equally effective in restoring a desired blood pressure,their individual working mechanisms seems to have different consequences on the macro and microcirculation.The effects of equipressor doses of norepinephrine and phenylephrine on elderly patients with minor comorbidities and on microcirculatory blood flow in the gastrointestinal tract have shown an increase in cardiac output(CO)and cardiac index(CI)in the norepinephrine group,whereas the phenylephrine group showed a decreased CO and CI.Differences in the cardiovascular response may lead to different effects on tissue oxygenation.Conclusion Phenylephrine and norepinephrine infusions were both safe to use for elderly undergoing radical resection of colorectal carcinoma surgery and the misconception that norepinephrine is dramatically different from phenylephrine is proved not correct.In fact,Phenylephrine can be used safely in the context of elderly ASA II or III with minor comorbidities.