Ignite Creation Date:
2024-07-17 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06499467
Status:
RECRUITING
Last Update Posted:
2024-07-12
First Post:
2024-07-05
Brief Title:
Norepinephrine Equivalent Dose of Vasopressin Phenylephrine and Epinephrine in Septic Shock
Sponsor:
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Organization:
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Study Overview
Official Title:
Norepinephrine Equivalent Dose of Vasopressin Phenylephrine and Epinephrine in Septic Shock Patients A Prospective Study
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Septic shock is the most common form of circulatory shock encountered in patients admitted in intensive care unit The initial management involves fluid resuscitation but if hypotension does not get resolved solely by it then vasopressors become the mainstay of the management of shock to maintain adequate mean arterial pressure MAP
Norepinephrine is recommended as the first line vasopressor in the management of septic shock as per Surviving Sepsis Campaign guidelines of 2021 It recommends addition of vasopressin to the regime if the target MAP is not achieved with just norepinephrine However in clinical practice various other vasopressors are being used in the management of septic shock as per clinical condition Different vasopressors have different modes of action and pharmacological effects on hemodynamics Therefore there evolved the need of development of a formula that would reflect the potency of each vasopressor in a standardized manner Thus the concept of Norepinephrine Equivalence NEE came into existence In the recent years different studies were conducted in various parts of the world with different primary objectives These authors have proposed different formulas for calculation Norepinephrine Equivalence NEE dose of the used vasopressors as an inference from their studies All these formulas are based on assumptions and there lacks standardization There are presently no studies available in the existing literature where a prospective study is done to primarily determine the Norepinephrine equivalence dose NEE of other vasopressors in patients of septic shock Hence the investigators aim to find out equivalent dose of these different drugs which are being used commonly in the management of septic shock in a prospective planned study
Norepinephrine is recommended as the first line vasopressor in the management of septic shock as per Surviving Sepsis Campaign guidelines of 2021 It recommends addition of vasopressin to the regime if the target MAP is not achieved with just norepinephrine However in clinical practice various other vasopressors are being used in the management of septic shock as per clinical condition Different vasopressors have different modes of action and pharmacological effects on hemodynamics Therefore there evolved the need of development of a formula that would reflect the potency of each vasopressor in a standardized manner Thus the concept of Norepinephrine Equivalence NEE came into existence In the recent years different studies were conducted in various parts of the world with different primary objectives These authors have proposed different formulas for calculation Norepinephrine Equivalence NEE dose of the used vasopressors as an inference from their studies All these formulas are based on assumptions and there lacks standardization There are presently no studies available in the existing literature where a prospective study is done to primarily determine the Norepinephrine equivalence dose NEE of other vasopressors in patients of septic shock Hence the investigators aim to find out equivalent dose of these different drugs which are being used commonly in the management of septic shock in a prospective planned study
Detailed Description:
Sepsis is a life-threatening state of organ dysfunction caused by dysregulated response of host to infection It is the most common form of circulatory shock encountered in patients admitted in intensive care unit In physiological state blood pressure is maintained by the interplay of three major mechanisms namely sympathetic nervous system vasopressin system and renin aldosterone system However in the states of vasodilatory shock these homeostatic mechanisms are disturbed The initial management involves fluid resuscitation but if hypotension doesnt get resolved solely by it then vasopressors become the mainstay of the management of shock to maintain adequate mean arterial pressure MAP
Norepinephrine has been recommended as the first line vasopressor for management of septic shock since 2004 and the latest guideline recommends addition of vasopressin along with norepinephrine when the target MAP is not achieved However in clinical practice various other vasopressors are used in the management of septic shock Different vasopressors have different modes of action and pharmacological effects on hemodynamics Therefore there evolved the need of development of a formula that would reflect the potency of each vasopressor in a standardized manner Thus the concept of Norepinephrine Equivalence NEE came into existence It is a scale to quantify the exposure to various vasopressors by converting their dose as an equivalent of norepinephrine It allows us to combine the dose of other vasopressors in a single scale and quantitatively assess the severity of shock when norepinephrine is being used along with other vasopressors
Annane et al conducted a study in 2007 in 330 patients of septic shock with the primary objective of comparing the efficacy and safety of norepinephrine plus dobutamine with those of epinephrine alone in septic shock They inferred from their study that the doses of vasopressors needed to achieve the MAP target were same for epinephrine and norepinephrine Similarly Myburgh et al studied in 280 patients of circulatory shock in the year 2008 to determine whether there was any difference between epinephrine and norepinephrine in achievement of MAP goal in the ICU patients and found that the maximal daily infusion of epinephrine and norepinephrine didnt have difference to achieve a target MAP De Becker et al conducted a study in 2003 on 20 septic shock patients with the primary objective to assess the effects of different doses of dopamine norepinephrine and epinephrine on the splanchnic circulation in patients of septic shock They found that the final infusion rate of epinephrine was 062 mcgkgmin which was comparable to 045 mcgkgmin rate of norepinephrine infusion to achieve the target MAP suggesting a conversion ratio of 141 Hussain et al found in their study on 42 patients of septic shock in 2014 to determine the efficacy of phenylephrine in comparison to norepinephrine in patients of septic shock in ICU that phenylephrine was 11 times equipotent to norepinephrine Gordon et al studied on 409 patients of septic shock in 2016 to compare the effect of early vasopressin versus norepinephrine on kidney failure They concluded from their study that 004Umin of vasopressin to be equivalent to 01 mcgkgmin of norepinephrine
Goradia et al proposed a norepinephrine equivalent formula in 2021 in their review article as Norepinephrine dose mcgkgmin epinephrine dose mcgkgmin 25 x vasopressin Umin 01 phenylephrine dose mcgkgmin Kotani et al proposed a different norepinephrine equivalent formula in 2023 as follows Norepinephrine dose µgkgmin epinephrine dose µgkg min 006 phenylephrine dose µgkgmin 25 vasopressin dose Umin
However since these calculations of NEE are based on assumptions and not standardized there are several different formulae for calculation of the same Different studies were conducted in different parts of the world with different primary objectives the authors proposed different NEE formulas of the used vasopressor as an inference from their studies
Presently there are no studies available in the existing literature where a prospective study is done to primarily determine the Norepinephrine equivalence of other vasopressors namely vasopressin phenylephrine and epinephrine in patients of septic shock Hence the investigators aimed to study the NEE dose of the commonly used vasopressors in the ICU in septic shock patients
During the study period all adult ICU patients having septic shock will be considered for inclusion Once the patient meets the inclusionexclusion criteria informed written consent will be obtained at the beginning of the study The weight of the patient will be noted from the weight-measuring beds and the drug preparations are made accordingly The transducer will be zeroed to the atmospheric pressure and baseline MAP will be recorded A second vasopressor will be connected to the central venous catheter CVC as per the standard preparation Then Norepinephrine infusion dose will be deescalated over 5-10 minutes by 01 mcgkgmin Simultaneously the dose of the second vasopressor will be titrated to achieve the baseline MAP 1 mmHg Two readings of the dose of the second vasopressor will be recorded at least 5 minutes apart and their mean will be calculated Evaluation with more than one vasopressor will depend upon the clinical condition of the patient as decided by the treating team However if more than one vasopressor are being assessed for NEE dose then the next drug will be assessed after at least one hour gap The same patient can be included for the study for more than once if they receive norepinephrine in three different dose ranges viz 01-05 mcgkgmin 05-1 mcgkgmin and 1 mcgkgmin
Demographic and clinical characteristics of included patients will be recorded in structured case report forms Candidates who qualify for the inclusion criteria will be included in the study The baseline MAP will be recorded The norepinephrine infusion will be tapered down gradually by 01 mcgkgmin and in the meanwhile a second vasopressor will be introduced to maintain the baseline MAP recorded at the beginning of the study After 15 minutes of stabilization of the dose of the second vasopressor two readings of the dose of the second vasopressor will be taken 5 minutes apart and their mean will be taken as a NEE of that particular vasopressor
Norepinephrine has been recommended as the first line vasopressor for management of septic shock since 2004 and the latest guideline recommends addition of vasopressin along with norepinephrine when the target MAP is not achieved However in clinical practice various other vasopressors are used in the management of septic shock Different vasopressors have different modes of action and pharmacological effects on hemodynamics Therefore there evolved the need of development of a formula that would reflect the potency of each vasopressor in a standardized manner Thus the concept of Norepinephrine Equivalence NEE came into existence It is a scale to quantify the exposure to various vasopressors by converting their dose as an equivalent of norepinephrine It allows us to combine the dose of other vasopressors in a single scale and quantitatively assess the severity of shock when norepinephrine is being used along with other vasopressors
Annane et al conducted a study in 2007 in 330 patients of septic shock with the primary objective of comparing the efficacy and safety of norepinephrine plus dobutamine with those of epinephrine alone in septic shock They inferred from their study that the doses of vasopressors needed to achieve the MAP target were same for epinephrine and norepinephrine Similarly Myburgh et al studied in 280 patients of circulatory shock in the year 2008 to determine whether there was any difference between epinephrine and norepinephrine in achievement of MAP goal in the ICU patients and found that the maximal daily infusion of epinephrine and norepinephrine didnt have difference to achieve a target MAP De Becker et al conducted a study in 2003 on 20 septic shock patients with the primary objective to assess the effects of different doses of dopamine norepinephrine and epinephrine on the splanchnic circulation in patients of septic shock They found that the final infusion rate of epinephrine was 062 mcgkgmin which was comparable to 045 mcgkgmin rate of norepinephrine infusion to achieve the target MAP suggesting a conversion ratio of 141 Hussain et al found in their study on 42 patients of septic shock in 2014 to determine the efficacy of phenylephrine in comparison to norepinephrine in patients of septic shock in ICU that phenylephrine was 11 times equipotent to norepinephrine Gordon et al studied on 409 patients of septic shock in 2016 to compare the effect of early vasopressin versus norepinephrine on kidney failure They concluded from their study that 004Umin of vasopressin to be equivalent to 01 mcgkgmin of norepinephrine
Goradia et al proposed a norepinephrine equivalent formula in 2021 in their review article as Norepinephrine dose mcgkgmin epinephrine dose mcgkgmin 25 x vasopressin Umin 01 phenylephrine dose mcgkgmin Kotani et al proposed a different norepinephrine equivalent formula in 2023 as follows Norepinephrine dose µgkgmin epinephrine dose µgkg min 006 phenylephrine dose µgkgmin 25 vasopressin dose Umin
However since these calculations of NEE are based on assumptions and not standardized there are several different formulae for calculation of the same Different studies were conducted in different parts of the world with different primary objectives the authors proposed different NEE formulas of the used vasopressor as an inference from their studies
Presently there are no studies available in the existing literature where a prospective study is done to primarily determine the Norepinephrine equivalence of other vasopressors namely vasopressin phenylephrine and epinephrine in patients of septic shock Hence the investigators aimed to study the NEE dose of the commonly used vasopressors in the ICU in septic shock patients
During the study period all adult ICU patients having septic shock will be considered for inclusion Once the patient meets the inclusionexclusion criteria informed written consent will be obtained at the beginning of the study The weight of the patient will be noted from the weight-measuring beds and the drug preparations are made accordingly The transducer will be zeroed to the atmospheric pressure and baseline MAP will be recorded A second vasopressor will be connected to the central venous catheter CVC as per the standard preparation Then Norepinephrine infusion dose will be deescalated over 5-10 minutes by 01 mcgkgmin Simultaneously the dose of the second vasopressor will be titrated to achieve the baseline MAP 1 mmHg Two readings of the dose of the second vasopressor will be recorded at least 5 minutes apart and their mean will be calculated Evaluation with more than one vasopressor will depend upon the clinical condition of the patient as decided by the treating team However if more than one vasopressor are being assessed for NEE dose then the next drug will be assessed after at least one hour gap The same patient can be included for the study for more than once if they receive norepinephrine in three different dose ranges viz 01-05 mcgkgmin 05-1 mcgkgmin and 1 mcgkgmin
Demographic and clinical characteristics of included patients will be recorded in structured case report forms Candidates who qualify for the inclusion criteria will be included in the study The baseline MAP will be recorded The norepinephrine infusion will be tapered down gradually by 01 mcgkgmin and in the meanwhile a second vasopressor will be introduced to maintain the baseline MAP recorded at the beginning of the study After 15 minutes of stabilization of the dose of the second vasopressor two readings of the dose of the second vasopressor will be taken 5 minutes apart and their mean will be taken as a NEE of that particular vasopressor
Study Oversight
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