Effects Of Prophylactic Infusion Of Methoxamine On Hemodynamics And Blood Gas In The Elderly Patients During Continuous Hyperthermic Peritoneal Perfusion

Background and ObjectiveGastrointestinal cancer is one of the serious diseases endangering human health.In the present, the incidence of gastric cancer is33.14/100000(The worldstandardized rate is23.09/100000) in Chinese, which is ranked second in allmalignant tumors. The mortality of gastric cancer is24.34/100000(The worldstandardized rate is16.39/100000) over the same period, which is ranked third in allmalignant tumors. The incidence of colorectal cancer ranks third and there is a risingtrend year by year in the world. Relapse and metastasis of peritoneal happen in themost postoperative patients with gastrointestinal cancer. The CHPP (ContinuousHyperthermic Pertioneal Perfusion) obtains better results in the prevention andtherapy of peritoneal metastasis after gastric cancer after radical resection of gastriccancer, which wins the broad consensus of scholars at home and abroad in recentyears. The heart rate increases, the mean arterial pressure decreases and obviousmetabolic acidosis appear because of the large number of perfusion liquid whichelevates the temperature in the CHPP. With the improvement of people’s livingstandard and the coming of aging in China, the proportion of the elderly people is more and more among patients with advanced cancer. Due to the changes inpathology, physiology and pharmacology of elderly patients and malnutrition as theresult of tumor itself, which cause hemodynamics fluctuations in elderly patientswith gastrointestinal cancer during the period of CHPP is more obvious. If notcorrected, it is likely to lead to serious cardiovascular and cerebrovascular accident.The present study for the CHPP during a series of physiological changes ismainly symptomatic treatment. When the patients have hypotension, the majority ofscholars give liquid with the use of vasoconstrictors, such asphenylephrine,dopamine, norepinephrine, ephedrine; the majority of scholarsgive beta blockers or calcium channel blockers when tachycardia occurs; themajority of scholars use NaHCO3and other basic drugs under the guidance of bloodgas when metabolic acidosis comes up. The shortage of blood volume caused by thebody high temperature and blood vessel expansion during CHPP call into beinga series of physiological changes. Methoxamine is a highly selective α1receptoragonist, on α2, β receptor almost had no effect. On the one hand,it shrinks afferentarterioles and increases systemic vascular resistance, aortic diastolic blood pressure,coronary perfusion pressure and myocardial blood flow due to excite α1receptorsarteriolar vasoconstriction; on the other hand, it is beneficial to the protection ofheart and improvement of myocardial hypoxia because it does not excite onmyocardium and cause myocardial oxygen consumption increase, slow down theheart rate and myocardial oxygen consumption through increasing blood pressure,which is especially advantageous for elderly patients. According to the physiologicchanges during CHPP, we assume that the liquid infusion is completed before CHPP,a small doses of methoxamine is infused after the beginning of CHPP and thevolume of liquid for maintain and loss because of body high temperature. Thepurpose of this experiment was to observe the hemodynamics changes and evaluatethe effect of prophylactic infusion of methoxamine on hemodynamics and blood gasin the elderly patients with CHPP through Vigileo hemodynamic monitoring systemand provide reference for clinical rational drug use. Materials and MethodsThirty adult patients of CHPP after gastrointestinal tumor resection, ASA gradeI or II, age65～80years old, no limitations to genders, body mass index is18kg/m2~25kg/m2. All the patients were randomly and equally allocated to two groups(n=15each): control group (C group) and methoxamine group (M group).Preoperative preparation: Nothing Per-os8hours. All patients included in trialsused nothing premedication before anesthesia. After entering the operating room,monitor vital signs of patients with Philips MP60monitor (Germany PHILIPSCompany), including blood pressure (BP), electrocardiogram (ECG) and pulseoxygen saturation (SpO2). Open peripheral venous access, puncture the left radialartery and right internal jugular vein catheterization under local anesthesia. Connectthe three generation FloTrac-Vigileo monitor (Edawards Lifesciences, CA, USA) tomonitor central venous pressure (CVP), cardiac output (CO), systemic vascularresistance (SVR) and stroke volume variation (SVV). Monitor anesthesia depth bymeans of the BIS monitor (A-2000America Aspect).Anesthesia methods: Induction of anesthesia is performed in two groups bytitrated infusion of midazolam(0.05mg/kg),sufentanil(0.3μg/kg),etomidate(0.3mg/kg)and rocuronium(0.6mg/kg).After muscle relaxant completely effective, inserted atracheal catheter and fixed position with satisfied breathing sound. Choose catheterwith inner diameter7.5for men and7for women. Mechanical ventilation aftertracheal intubation, respiratory parameters for VT8~10ml/kg, RR10~15beats perminute, respiratory ratio1:2, maintain PETCO2between35~45mmHg(1mmHg=0.133kPa). Anesthesia was maintained by target controlled infusion ofpropofol (2~4.0ug/ml), remifentanil (2~6.0ng/ml), constant speed infusion ofcisatracurium besilate for injection (1~2ug-1kg-1min-1). The objective for liquidinfusion during radical resection of tumor is maintain SVV＜13%. Regulate plasmaconcentration of propofol and remifentanil according to the BIS monitor (A-2000America Aspect), maintaining the BIS value at50～60. Stop the infusion ofremifentanil and inject sufentanil at0.15ug/kg before CHPP, maintenance ofanesthesia with target controlled infusion of propofol. Group M infusesmethoxamine at the rate of40ml/h, concentration of0.15mg/ml and group C infuses normal saline at the beginning of CHPP. Put ice in both sides of patients’ bilateralneck to reduce the intracranial temperature. Inject methoxamine2mg when thepatients have hypotension (SBP less than80%of the basic value or＜90mmHg).IfHR＜50beats per minutes, inject atropine0.3~0.5mg, but when the HR＞100beats per minutes, intravenous inject esmolol0.5mg/kg.Outcome measures: Monitor and record the values of HR、SBP、DBP、CO、CVP、SVR、SVV before the CHPP (T1), at the beginning of CHPP5min (T2),15min (T3),30min (T4),60min (T5) and after CHPP30min (T6) in hemodynamicsand PH, BE, PO2, PCO2before the CHPP (T1), CHPP30min (T4),60min (T5) inblood gas. The frequence of hypotension(SBP less than80%of the basic value or＜90mmHg) and tachycardia （HR＞100beats per minutes）or bradycardia （HR＜60beats per minutes）was also recorded.Statistical treatment: Statistical software package (SPSS16.0) was used for dataanalysis. The numerical data variables expressed as mean±standard deviation. Thefactor within-subject at different time points were analysized with variance forrepeated measures data and the factor between-subject were compared using thegroup t test. The count data was with Fisher’s exact test. The statistical significancetest criterion is α=0.05.ResultsThe differences between groups were not statistically significant (P＞0.05) inage, height, weight, volume of fluids, bleeding volume and the time from thebeginning of operation to the end.Systolic blood pressure (SBP): Compared with T1, C group increased at T2(P＜0.05), decreased in T4~T6(P＜0.05); M group increased at T2(P＜0.05),decreased at T6(P＜0.05). Compared with T2, C group decreased in T3~T6(P＜0.05), M group decreased in T4~T6(P＜0.05).Compared with C group, M groupincreased in T4and T5(P＜0.05).Diastolic blood pressure (DBP): Compared with T1, C group increased at T2(P＜0.05), decreased in T4~T6(P＜0.05); M group increased in T2and T3(P＜0.05), decreased at T6(P＜0.05). Compared with T2, C group decreased in T3~T6(P＜0.05), M group decreased in T4~T6(P＜0.05).Compared with C group, M groupincreased in T4and T5(P＜0.05).Heart rate (HR): Compared with T1, C group increased in T2~T6(P＜0.05); Mgroup increased in T2and T6(P＜0.05). Compared with T2, C group increased inT4and T5(P＜0.05), M group decreased in T3~T5(P＜0.05).Compared with Cgroup, M group decreased in T4and T5(P＜0.05).Cardiac output (CV): Compared with T1, C group and M group both increasedin T2~T6(P＜0.05). Compared with C group, there was not statistically significant(P＞0.05) between the two groups at each time point.Central venous pressure (CVP): Compared with T1, C group and M group bothincreased in T2~T5(P＜0.05). Compared with T2, C group decreased in T4~T6(P＜0.05), M group decreased at T6(P＜0.05). Compared with C group, there was notstatistically significant (P＞0.05) between the two groups at each time point.Systemic vascular resistance (SVR): Compared with T1, C group decreased inT2~T5(P＜0.05), M group decreased both in T2and T6(P＜0.05). Compared withT2, C group decreased in T3~T6(P＜0.05), M group decreased in T6(P＜0.05).Compared with C group, M group increased in T3~T5(P＜0.05).Stroke volume variation (SVV): Compared with T1, C group and M groupdecreased in T2~T5(P＜0.05). Compared with T2, C group and M group bothincreased at T6(P＜0.05). Compared with C group, there was not statisticallysignificant (P＞0.05) between the two groups at each time point.PH (PH): Compared with T1, C group and M group both decreased at T5(P＜0.05). Compared with C group, there was not statistically significant (P＞0.05)between the two groups at each time point.Base excess (BE): Compared with T1, C group and M group both decreased atT5(P＜0.05). Compared with C group, there was not statistically significant (P＞0.05) between the two groups at each time point.The partial pressure of oxygen (PO2): Compared with T1, there was notstatistically significant (P＞0.05) at each time point in both groups. Compared withC group, there was not statistically significant (P＞0.05) between the two groups at each time point.Partial pressure of carbon dioxide (PCO2): Compared with T1, C group and Mgroup both increased at T5(P＜0.05). Compared with group C, there was notstatistically significant (P＞0.05) between the two groups at each time point.Hypotension: C group occurred in8cases (53%), M group occurred in1case(7%). Compared with group C, the incidence of group M reduced (P＜0.05).Bradycardia: C group occurred in0cases (0%), M group occurred in1case(7%). Compared with group C, there was not statistically significant (P＞0.05)between the two groups.Tachycardia: C group occurred in5cases (33%), M group occurred in0cases(0%). Compared with group C, the incidence of group M reduced (P＜0.05).Conclusion1. Systemic vascular resistance decreased is the mainly change of hemodynamicin elderly patients during continuous hyperthermic peritoneal perfusion.2. The prophylactic infusion of methoxamine could helps keeping a moresteady hemodynamics for the elderly patients during the CHPP, reducing the adverseeffects and decreasing the risk of anesthesia.3. It does not have significantly effect on blood gas through methoxamineinfusion to increase tissue perfusion, so the optimal rate and other factors have to beexplored.