A clinical study on the prevention of phlebitis caused by Cinobufagin using hand exercise combined with Jinhuang ointment

Yan-Li Min,Yan-Ping Wang＊

1Department of Oncology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,China.

Abstract

Keywords:Hand exercise,Jinhuang ointment,Cinobufagin,Phlebitis

Introduction

Cinobufagin is a hydrophilic Chinese traditional medicine having the whole skin of Bufo gargarizans that is dried in the shade as the main ingredient [1].With the in-depth study on its pharmacological effects,it was confirmed that cinobufagin has antiviral,anti-inflammatory, and analgesic effects as well as immune regulation and antitumor effects.Chinese medicine therapy mainly based on cinobufagin has shown satsifactory clinical results in the treatment of advanced cancers[2].However,its characteristics such as high viscosity,slow drip rate, and vascular irritation of cinobufagin will cause an adverse reaction, such as redness,swelling, pain,and phlebitis.The incidence of phlebitis among the adverse reactions of cinobufagin is 21.39%.Among the reactions, the most common is vascular irritation, which exhibited as vasospasm pain,redness at the IV site,acupuncture-like pain,and streak formation at the IV site [3].In some severe conditions,the patient cannot tolerate and discontinue the infusion.Therefore, it is important that the cinobufagin application lessens the incidence of phlebitis.In this study, we assessed the preventive effect of hand exercise combined with jinhuang ointment inunction on phlebitis caused by cinobufagin.

Method

Subjects

We have chosen 90 cases of tumor patients who were hospitalized in the Department of Oncology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.They all received an IV infusion of cinobufagin from May 2018 to June 2019.All three groups of patients have received peripheral venipuncture with the same type and size of the IV infusion set.The patients were then divided into three groups with the use of the random number table method:30 cases in the control group, 30 cases in the jinhuang ointment group, and 30 cases in the group of hand exercise combined with jinhuang ointment.

Inclusion criteria

The inclusion criteria are as follows:patients diagnosed with a malignant tumor and who received an IV infusion of cinobufagin; without consciousness disorder and mental disorder; without hand fracture history; cooperation for the nursing; no local skin lesion and other inflammatory reactions; self-care ability score above 80 points; no superior vein cave syndrome;and no allergy history for jinhuang ointment and adhesive plaster.All the patients have signed the informed consent form.

Exclusion criteria

The exclusion criteria are as follows:Allergy history for jinhuang ointment and adhesive plaster; hand fracture history; local skin lesion and other inflammatory reactions; consciousness disorder and mental disorder; impaired verbal communication; and Peripherally inserted central venous catheters, Central venous catheterization and Implantable central IV port.

Treatment

From the first day of hospitalization, patients in the control group were given routine nursing before IV infusion of cinobufagin, such as medication guidance,psychological care,and IV care.With the conventional group in mind, the jinghuang ointment group received the hospital preparation of jinghuang ointment for inunction, the ingredients of which are Jianghuang(Turmeric), Dahuanggen (Rhubarb root) , Huangbai(Phellodendri Cortex), and Chenpi (Citri Reticulatae Pericarpium).The jinghuang ointment has anti-inflammatory,detoxification,and analgesic effects.Before the IV infusion of cinobufagin, patients used the jinghuang ointment to moisten evenly the area 2-3 cm above the IV site, with a thickness of 1-2 mm.The ointment was covered with gauze, fixed with an adhesive plaster,qd,and kept for 6 hours.The cycle is one week.The combined group performed hand exercises excluding the jinghuang ointment.The training for hand exercises was conducted by nurses with a bachelor’s degree who have applicable training knowledge and good communication skills.

The combined group composed of 30 patients watched the video in the classroom,and to instigate the efficacy and techniques of hand exercise, a WeChat platform was set up.Patients were informed to do the hand exercise daily; for example, they can practice from 8:00 am to 9:00 am, for about 10 minutes.This exercise is altered based on the rehabilitation exercise at the early stage designed by Zhang XJ,et al.[4].The specific methods are as follows:in the first section(one-handed fist movement in the meantime), stretch out both arms, make both arms perpendicular to the body,squeeze hands slowly and firmly as inhaling,and slowly open hands from the little finger to the thumb as exhaling.In the second section (move your hands into crossed fists), clench your crossed hands tightly;stretch your arms out straight, cross your fingers, and keep your palms straight out as inhaling; retract and clench the fists, and press the opposite side of the valley by your index finger and thumb as exhaling.In the third section (rub the hands together), the opisthenars of your hands are rubbed against each other for the Sanyang meridian from the bottom to the top as inhaling, while the palms of the hands are rubbed against each other for the Sanyin meridian from top to bottom as exhaling.In the fourth section (arm hold movement), hold your opposite arms together firmly, from fingers, wrists, to elbows.The tracking record is as follows:The duty nurse did the implementation and recording.The head nurse did the tracking, asking about the implementation, and checking the installation of cinobufagin at any time.Apart from that, the head nurse also kept providing help for the potential problem, pointing out the improvement at any time, and summarizing the implementation.

Efficacy evaluation

The efficacy is evaluated in accordance to the phlebitis grading standard of the Infusion Nurses Society into four grades.Grade I, slight pain at the IV site, redness, and/or swelling, with no streak formation and no indurations touched; grade II, moderate pain at the IV site, local redness, slight swelling, streak formation, and no indurations touched; grade III,severe pain at IV site and surrounding tissues,moderate swelling, blister formation at the local skin,streak formation,and palpable induration;and grade IV,continuous pain at IV site and surrounding tissues,moderate to severe swelling, blister formation, and severely compromised limb function[5].

The numerical rating scale (NRS) was used to assess the pain intensity as follows.painless (0), slight pain(pain does not affect sleep, 1-3), moderate pain (pain affects sleep, 4-6), severe pain (cannot fall asleep or wake up in sleep,7-10)[6].

Statistical analysis

The data obtained were the number of cases and percentages (%).The SPSS 21.0 software was used to process the data.A chi-square test was used to compare the rates.P＜ 0.05 means there is a statistically significant difference.

Results

Overall of enrolled cases

In this study, 90 patients were finally enrolled, which include 30 cases in the control group, 30 cases in the jinhuang ointment group, and 30 cases in the hand exercise combined with the jinhuang ointment group.In the groups, there were 46 males and 34 females,aged 48-78 years (mean:15.18).Among the three groups of patients, there were no statistically significant differences in age, gender, self-care ability,treatment,and intravenous infusion set(P＞0.05).

Inhibition of phlebitis by hand exercise combined with jinhuang ointment

The results have shown that after treatment for 1 week,the incidences of grade I/II phlebitis in the control group, the jinhuang ointment group, and the group of hand exercise combined with jinhuang ointment were 53.5%, 23.3%, and 10%, respectively.There was a significant decrease in the jinhuang ointment group and the combined group as in comparison with the control group(P=0.0169,P=0.0003).

Even if the incidence of phlebitis in the combined group was lower than that of the jinhuang ointment group, no statistically significant difference (P=0.1659)was found.

The incidences of grade III/IV phlebitis in the control group, the jinhuang ointment group, and the group of hand exercise combined with jinhuang ointment were 23.3%, 3.3%, and 3.3%, respectively.The jinhuang ointment group and the combined group had significantly lower incidences than that of the control group (P=0.0003,P=0.0227).There was no difference in values between the combined group and the jinhuang ointment group(Table 1).

Table 1:Comparison of the incidence of phlebitis among groups

Table 2:Comparison of the incidence of pain among groups

The effect of hand exercise combined with jinhuang ointment on the pain

After treatment for one week, the incidences of pain in the control group,the jinhuang ointment group,and the group of hand exercises combined with jinhuang ointment were 56.7%, 36.7%, and 20%, respectively.No significant difference was found between the jinhuang ointment group and the control group (P=0.1205); the combined group has shown a significant decrease compared with the control group(P=0.0035);the incidence of pain in the combined group was lower than that of the jinhuang ointment group,but there was no statistical difference(P=0.1520)(Table 2).

Discussion

Phlebitis is an inflammatory chemical reaction on the local vein.It is due to irritation from drugs with a high concentration in the vein or from the prolonged insertion of central catheter.Indolylalkylamine alkaloid, which is the main component of cinobufagin injection, can directly stimulate the norepinephrine release by stimulating adrenergic nerves and thus lead to vasoconstriction.The serotonin has strong contraction and stimulating effects on the blood vessel,which result in vascular endothelial cell damage,inflammatory infiltration, and even fibrous tissue hyperplasia.The different indurations and obstructions can be found on the venous vascular wall[7].Phlebitis compromises the patients’ quality of life.In some serious cases, the patients have to stop the infusion,affecting the treatment.Therefore, the reduction of phlebitis incidence will improve the patients’quality of life and clinical efficacy.

Traditional Chinese medicine has a belief that phlebitis belongs to the acute thrombophlebitis category.Acute thrombophlebitis caused by cinobufagin can damage the local veins, resulting in poor blood flow,blood stasis, and stagnation of Qi and blood which may bring about pain.The blocked Qi and blood delivery caused the agglomerate on the skin; the blocked fluid distribution led to swelling; a local fever will occur after prolonged blood stasis; the vein damage, blood within the skin, and the heat will produce local redness [8].In the making of the jinghuang ointment, rhubarb root and rhizome can remove the toxin, remove heat to cool blood, and eliminate stasis; Huangbai (Phellodendri Cortex)clears away heat and dampness; turmeric can be used to activate blood and dissolving stasis and reduce swelling and pain; Tiannanxing (Arisaema heterophyllum Blume) reduces swelling and pain;Changshu (Swordlike Atractylodes) rhizome clears away heat and dampness; and Chenpi (Citri Reticulatae Pericarpium) facilitates the Qi, dissipating stasis, and relieving pain.Apart from that, the Baizhi(Angelicae dahuricae radix) facilitates the Qi,activating collaterals, dissipating stasis, promoting blood circulation, releasing orifices, and reducing swelling and toxicity.Jinghuang ointment has been conveniently and efficiently formed with honey as the excipient, and it can be used directly to moisten the local skin for dissipation of stasis and inflammation,in order to achieve the purpose of treatment [9].Jinghuang ointment has been widely used in clinical practice, but the patient still experienced pain,redness,and swelling at the IV site.In some cases, unpalpable veins on the opisthenar are the cause of difficulty in performing venipuncture, which hurts not just the patient but also the nurse.The focus of current research is to improve further the therapeutic effect of jinhuang ointment.

Chinese medicine believes that the meridian is a system of “inner organs and outer limbs.” It functions as the bridge of the inside and the outside, connecting the limbs, running Qi and blood, and nourishing the whole body.The three Yin meridians of the hand goes from the human chest to the fingers.At the same time,the three Yang meridians of the hand start from the opisthenar to the head, allowing the yin and yang converge at the finger end.Hand exercise is done to utilize the flexion and extension of joints and muscles with breathing, thus stimulating the meridian of both hands, promoting blood circulation, and enhancing the flexibility of veins.Hand exercise can promote blood return to the upper extremity through muscle contraction,and the muscle tension changes with fixed muscle length[10].After exercise,the local blood flow is increased,improving not only the slow venous blood flow in the upper extremities but also the phlebitis caused by the adhesion of cinobufagin to the vein.Hand exercise also incorporates breathing training,which enhances the muscle strength, endurance, and coordination of the breathing muscles.Aside from that,it can improve the thoracic activity, strengthen the patient’s chest breathing ability, and enhance the negative pressure in the chest cavity.Through clinical practice, it has been shown that the hand exercise is a rehabilitation exercise, combining the human body and nature with breathing based on the theory of Chinese medicine.It is simple, practicable, and popular among patients with good compliance.

In this study, we found that the incidence of phlebitis (grade I/II, III/IV) due to cinobufagin was lessened in both jinghuang ointment group and hand exercise group, and the combined group showed a trend of better efficacy.The hand exercise combined with jinghuang ointment group also significantly reduced the incidence of pain, and the combined group’s effect was better than the others.

In the recent years, the development of the clinical medical field witnesses the growing importance of health exercises.In the field of nursing research, hand exercise is also a key content.The results of this study show that hand exercises together with jinghuang ointment inunction have a good effect on phlebitis caused by cinobufagin with a simple procedure and good compliance.However, this study is limited to a small sample size and a short period for observation and intervention.In the future studies,we will consider increasing the sample size and patient compliance,performing follow-up after discharge to understand the long-term effect of this exercise.