Cold Pressor Test, Moderate Anaemia in Second and Third Trimester of Pregnancy

Background: 2 nd & 3 rd trimester of pregnancy is associated with profound adaptive autonomic cardiovascular changes. Anaemia in pregnancy, which is a common problem in India is known to put pregnant female at higher cardiovascular risk. Objective: The aim of this study is to measure & compare DBP response to CPT in both trimester in both control group & pregnancy with moderate anaemia (Case) for screening & diagnosis of autonomic imbalance. Method: After measuring vitaldata, anthropometric data, DBP response to CPT were measured & compared among control & case group (13-39 weeks of gestation) in sitting position. Result: A highly significant difference in Wt, SBP, DBP were observed in control group of 2 nd trimester when compared with 3 rd trimester. A highly significant difference was observed in Wt, DBP, DBP response to CPT of case group of 2 nd trimester when compared with 3 rd trimester; A highly significant difference was observed in Hb, SBP, DBP of case group of 3 rd trimester when compared with control group during 3 rd trimester of pregnancy;The chi-square test value shows that the observed DBP response to CPT in moderately anaemic pregnancy during 2 nd & 3 rd trimester is not due to chance. Conclusion: This study has found CPT as simple, safe, cost effective, reliable test aiding to understand pathophysiology of anaemia during late gestation. It is also useful tool to predict & screen high risk pregnancy among anaemic pregnancies for early intervention.


Introduction
A pre-eclampsia prevalence is of 7.5% of all pregnancies & it was found tobe slightly higher in primigravida 1 pregnancy with anemia 2,3 , forms the base of doing our study in primigravida. Rang et al argued that since a higher sympathetic nervous activity has been observed in pre-eclampsia, changes in autonomic control preceding the onset of pre-eclampsia could provide early identification & it is essential for prophylactic interventions to reduce morbidity & mortality associated with this syndrome explains the aim of performing this study. 4,5 Different studies have been performed about the etiology of pre-eclampsia but there is no reliable & cost-effective screening test. 6,7 Although inflammation & extensive endothelial dysfunction of vessels are the main possible mechanisms of pre-eclampsia, but the pathogenesis of this syndrome has not been well understood. 6 Conducting this study in pregnant women with anaemia will aid to understand pathogenesis of this syndrome. The cold water causes stimulation of cold & pain receptors in the hand. The information is carried to the brain through spinothalamic pathways. The reflex involves, rise in sympathetic outflow to the vasculature & heart resulting in rise in BP. 8  • Females with pregnancy induced complication (e.g. Hypertension, Diabetes, Pre-eclampsia, Toxaemia of pregnancy).
Subjects were explained the procedure & were asked to avoid tea, coffee, food 2 hrs. prior to study. Anthropometric Data (height, weight) were measured on Standard Measuring Scale. Vital Data temperature, pulse rate, BP were assessed in supine position. CPT (cold pressor test): The test is performed in sitting position. 8 Digital BP instrument was calibrated with standard sphygmomanometer. First the baseline BP was measured using digital BP instrument & then the subject was instructed about the test. Cold water of 10°C was prepared & maintained at that temperature. The subject was asked to immerse the hand in water up to the wrist for 1 min. without touching the bottom of the cold water bath. After that the hand was removed from the water & it was covered with towel. The DBP was measured in contra lateral arm just before the hand was taken out of water. The DBP was taken again at 1.5 min & 4 min after the hand was withdrawn from the cold water. Highest DBP value was considered for calculation. Data were analysed using licensed SPSS 16.0 software. Statistical tests In dependant t-test, ANOVA (Mann-Whitney test), Chi-square test were used to analyse the obtained data. Results were considered significant at p value<0.05 & highly significant at p value<0.01.
Observation:     20 , which is consistent with finding of our study. Total Peripheral Resistance (TPR) falls Significantly by at least 6 weeks of gestational age & reaches a Nadir of 40% below Non-pregnant Values by mid-gestation. Fall in TPR also makes CO to fall. The CO depends on patient position & is greatest when measured in Lateral Recumbent position. This is most notable during last Trimester. When, with the woman in supine Position, the gravid uterus & foetus impede venous Return (VR)to the heart. There is decrease inCO by 0.6 L/min in supine position. There is selective regional distribution of this Physiologic increase inCO. Uterine blood flow increases 10 fold to between 500 to 800 ml/min. Renal Blood Flow increases significantly by 50% during Pregnancy. 21,22 BP decreases in Pregnancy beginning as early as 7 th week. This early drop probably represents incomplete Compensation of the fall inTPR by the increase in CO. When measured in Sittingor Standing positions, SBP remains relatively stable throughout Pregnancy, whereas DBP decreases by a maximum of 10 mm Hg at 28 wks of gestation & then increases towards non-pregnant levels by term. In left Lateral position both decreases below Non-pregnant values at 24-32 wks of gestation 23,24 ; which is not included in our study. The rise in Systemic Resistance & fall in CO without change in Arterial Pressure observed after assumption of the Upright posture in adult imply Peripheral Vasoconstriction & indicate that the circulatory changes of chronic Anaemia are labile rather than fixed. 25 explains the need to select stress test like CPT for our study group. The reduced BP response reported could be due to antagonistic effect of the products of the utero Placental unit, such as progesterone or a diminished Contractile Response of the blood vessels to Adrenaline 26 probably explains the low DBP response than the cutoff value while performing CPTin both the groups. No Significant difference in pulse rate observed in our study. Data suggested that Tachycardia & Increased flow Velocity are not physiologically adapted to prolonged strain but rather are mechanisms to meet acute bodily stresses such as fever,exercise, hyper metabolism & acute anaemia. 25 William B Porter et al 25 has described four mechanisms operating in anaemic patients which may increase the supply of oxygen to tissues when the oxygen carrying capacity of the blood is reduced;under conditions of rest, a rapid velocity flow & tachycardia with an increase in minute volume of CO is the first response to anaemia. As compensation develops, tachycardia & increased velocity flow are largely replaced by selective Shunting of blood & the removal of an increasing percentage of Oxygen in the tissue capillaries from each gram of circulating Hb. A reduction in TPR reduces cardiac work, thus tend to balance the effect of the elevation in CO. In patients with highest CO, tachycardia was not a prominent feature. Even breathing 100% oxygen show no change in elevated CO in anaemia. 25, 27 this supports our study result;the high SBP & low DBP observed during 3 rd trimester of pregnancy with moderate anaemia. Martin et al 25 revealed that the severity ofChronic anaemia didnot correlate well with the level ofCO.They also revealed that the mean Venous Pressure was within normal limits for the anaemic Group & generally was unchanged after the therapy of Anaemia. The decreased Arterial Pressurein Anaemia might be a reflection of a number of events including generalised Vasodilatation & a reduced Bloodvolume. Maintenance of a normal Venous Pressure may well represent an effort to overcome these latter changes by Vasoconstriction & increasing the return of blood to the heart. The acute, immediate reversal of the high Output state of Anaemia by orthostatic Stress or by vasoconstrictor Drug indicates that the increased Blood flow is primarily mediated by lowered Peripheral Resistance due to vasodilatation rather than to low Blood Viscosity. 28,29 It has been postulated that the Hyperkinetic Response to anaemia in patients at rest occurs only when the Concentration of Hb falls beneath 7 gm/dl 30 explains the role of CPT to find out underlying Subclinical pathogenesis. Martin Duke et.al. 25 had revealed that in many patients, the hemodynamic values that appeared within normal limits in the Anaemic state were actually Altered when compared to that particular individuals normal state after therapy;explains the objective of performing this study.

Conclusion
This study has found CPT as simple, safe, cost effective, reliable test aiding to understand Pathophysiology of Anaemiaduring Late Gestation. It is also useful tool to Predict & Screen high risk Pregnancy among Anaemics for early Intervention. Many such studies & further evaluation are needed to support our observation forms the limitation of our study.
Ethical Clearance: Taken from ethical committee of smimer medical college and hospital.