Nursing Care in Patients with Ectopic Pregnancy who Under Go-On Fast tract Surgery: 2 Case Study

Yarnprasert P and Khetpanya T

Published on: 2024-05-04

Abstract

Background: Ectopic pregnancy was a high-risk of gynecological emergency and complicated to manage. If the fallopian tube ruptures, it will cause of shock from intra-abdominal hemorrhage, which can be life-threatened. Therefore, there must be closed and continuous care and observation by nurses in caring when there discharge according to nursing standards.

Objective: Comparative 2 case studies in nursing care for patients with ectopic pregnancies undergoing surgery in fast-track surgery according to nursing standards.

Methodology: This comparative case studied use case studied descriptive research methodology design to compare nursing process in fast tract surgery in ectopic pregnancy. Select case with purposive sampling who diagnosis with ectopic pregnancy and there visit in Kalasin hospital from April to July 2022 whole 2 case. Data collective with personal data collective form, observative form, in-dept interview form, Gordon's functional health patterns, medical record, a satisfaction questionnaire. Data analysis with descriptive, nursing diagnosis, nursing care and nursing outcome from first visit until discharge.

Result: Case studied 1 was a married Thai woman 26 years old G2P0A1L0 last 3 years visit at Kalasin hospital present with abdominal pain Rt. lower quadrant investigate by ultrasound found ectopic pregnancy with rupture Rt. fallopian tube with shock go on fast tract surgery post-operative good recovery and good conscious no complication length of stay 3 days. In case studied 2 was Thai women 25 years old G3P2A0L2 post sterilize visit at Kalasin hospital present with lower abdominal pain left side with vaginal bleeding, urine pregnancy test was positive, ultrasound found ectopic pregnancy in left fallopian tube no rupture go on fast tract surgery on time post-operative in fast tract surgery good conscious and recovery no complication, length of stay 3 days In summary from table 3 found that health problem all of 2 cases was similar 1)Hypovolemic shock related to abdominal bleeding evidenced by ultrasound found ectopic pregnancy with rupture Rt. fallopian tube with blood loss 2) Acute pain related to tissue injury from rupture ectopic pregnancy evidenced by grimacing, expression of pain and abdominal guarding. 3. Uncomfortable due to abdominal distension secondary to the operation received. 4. Risk to complication after surgery evidence by post-operative salpingectomy and 5. Risk for Infection related to tissue injury from surgery. In addiction differentiate nursing diagnosis between case study 1 and case study 2 was 1. Anxiety related to stress as evidenced by increased tension, apprehension, and expression of concern regarding upcoming surgery 2. Grieving and loss due to loss of pregnancy evidenced by ectopic pregnancy and rupture fallopian tube that problem was found in case study 1 but case study 2 was none

Conclusion: The nursing outcome found that nursing care had been closely provided via expert nurses based on patient’s conditions to correct the shock. Finally, patient was safe from shock and other mentioned health problems. In addiction differentiate of nursing diagnosis between 1st and 2nd case were anxiety case studied 1 was done related illness and operative but case studied 2 none because her experience in two time of caesarians section and own sterilized. Nursing care had been closely provided via expert nurses based on patient’s conditions to correct the shock. Finally, patient was safe from shock and other mentioned health problems

Suggestion: In summary of this studied more over the result can use for data base for research instance research and development, quasi-experimental-research or can use result for developed for clinical nursing practice guideline

Keywords

Case Study; Ectopic Pregnancy; Fast Tract Surgery; Nursing Care

Introduction

Ectopic pregnancy was any pregnancy implanted outside the uterine cavity In the UK the incidence is approximately 11/1,000 pregnancies, with approximately 11,000 ectopic pregnancies diagnosed each year1. Ectopic pregnancy was a high-risk of gynecological emergency and complicated to manage. If the fallopian tube ruptures, it will cause of shock from intra-abdominal hemorrhage, which can be life-threatened. Therefore, there must be closed and continuous care and observation by nurses in caring when there discharge according to nursing standards [2].

In Thailand, an incidence of 1-2 percent of pregnancies is found, with 95-98 percent occurring in the fallopian tubes, which are mostly located in the fallopian tubes. The ampulla is 12-13% located in the isthmic and fimbria, while the interstitial is 2-4%. In addition, it is located in the ovaries, cervix or in the abdominal cavity. (Less than 1 percent) [3] Ectopic pregnancy is considered a gynecological emergency. In general, treatment is divided into Supportive follow-up treatment with drugs and surgery, although nowadays there is a trend of increasing the use of drugs to treat ectopic pregnancy. And new drugs have been developed and used to treat ectopic pregnancies, but surgical treatment is still a popular method. Got good results there is a low recurrence rate And has high safety [4].

In patients (Pt.) with ectopic pregnancy who require surgical treatment, close supervision is required from the beginning and continuous monitoring because ectopic pregnancy is considered a gynecological emergency. Which is extremely difficult and complicated to care for especially patients who require urgent surgery under the Fast Tract Ectopic Pregnancy surgery system, which is still new in Thailand. Public health personnel or the team providing care therefore need to have very high knowledge, abilities, skills, and expertise. In particular, nurses, who are the closest caregivers to patients, need to develop necessary competencies in all four areas. Therefore, educators have a need to study the roles of advanced nurses and appropriate nursing care in patient care. Ectopic pregnancy that was surgically treated in the fast-track system this will lead to the determination of policies, guidelines, or models of care at both the hospital level and the national level [5].

Ultrasound is the gold standard for diagnosis of ectopic pregnancy with a specificity and sensitivity previously described as 94% and 87% respectively. The abdominal-pelvic nuclear magnetic resonance imaging (MRI) may help guide the involvement of adjacent organs [5].

Fast Track Surgery: FTS or Enhanced Recovery after Surgery: ERAS explain by Kehlet, H. (1990) main point of program was early rehabilitation of patients under collaboration of multidisciplinary with many model or multiple or multiple of techniques. Committed for decrease of abnormality and mobility after surgery. However, the treatment in ectopic pregnancy brought up to Fast Track Surgery: FTS or Enhanced Recovery after Surgery: ERAS for utilization get to safety in patients [6].

Objective

Comparative 2 case studied in nursing care for patients with ectopic pregnancy undergoing surgery in fast-track surgery according to nursing standards.

Purpose

  • Get to fast tract surgery in ectopic pregnancy nursing care guideline in organization
  • Explain and utilizations in organization and outside to international

Importance of study

Ectopic pregnancy was a crisis in gynecology, many complicated of care in individual and family care all of mental, emotional and social especially who undergo on surgery there want to closeup of care when first visit until discharge and continue to home care.  Management depends on maternal symptoms and fetal status. In many cases, emergency laparotomy is the chosen technique, as the patient may present acute, severe intra-abdominal hemorrhage due to placental separation of the implantation bed. Due to the extreme risk of complications and associated maternal mortality of up to 5 per 1000 cases, some experts recommend surgical intervention as soon as the diagnosis has been made. Cases of conservative management are usually isolated and fetal mortality can reach more than 50%. Abdominal pregnancy has also been associated with congenital malformations in about 20% of neonates [5].

Material and Methods

This comparative case studies use for descriptive research methodology design to compare nursing process in fast tract surgery in ectopic pregnancy. Select case with purposive sampling there arrive to visit in Kalasin hospital from April to July 2022 get to 2 sample sites. Data collective with personal data collective form, observative form, in-dept interview form, Gordon's functional health patterns, medical record, a satisfaction questionnaire. Data analysis with descriptive, nursing diagnosis, nursing care and outcome. The comparison of nursing diagnosis by evaluate health status using patient assessment concepts. According to Gordon's 11 health pattern to find problems and health needs bring to analyze problems and respond to needs in nursing practice to have quality that covers promotion, prevention, treatment, rehabilitation of health and use nursing process as key success for nursing practice. Since for the time first visit until discharge during the study period significant nursing problem where into 3 phases: preoperative postoperative and discharge planning.

Personal History

Case study 1: Thai female 26 years old 1st visit present with chief complaint abdominal pain 1 week. Pass History of Illness (PHI) 1 week Pre Time-Admit (PTA) abdominal pain at middle line paroxysm. The last of menstruation was 2 weeks ago abnormally present with 2 days and present of blood clot but a normally was 5 days no blood clot glavida3 Para 2 abortion 1 (ectopic pregnancy) Labor 2 last 7 years. Refer to Kalasin hospital on 9 April 2022 1.36 p.m. At ER good conscious mild pale conjunctival, right lower quadrant and left lower quadrant tenderness, no guading v/s was show   BP 114/80 mmHg. PR 68 bpm. RR 20 bpm. BT 37.0 C. UPT positive beta HCG result 53,621 Hematocrit (Hct.) 26.1% U/S was seen empty uterus, rupture left tubal pregnancy free fluid estimate 500 ml. Shock was identified get to manage shock sign then set operation for exploratory laparotomy with left salpingectomy under general anesthesia. In operation room was found left tubal pregnancy with rupture site at fimbria estimate of hemoperitoneum about 300 ml. normal looked of right ovary and fallopian tube, normal looked of left ovary. V/s BP 120/80 mmHg, PR 90 bpm, RR 18 bpm. (On ventilator) and BT 37.0 C. Post operation good conscious no bleeding per surgical wound no complications and sign of shock not found transfer to Gynecology ward for observe. At ward Pt. good conscious V/S was show BT 36.6-37.7 C., PR. 80-92 bpm. RR 20 bpm. BP 104/70-126/72 mmHg., no constipation plan for discharge on 12 April 2022 rang of stay 4 day and appointment 4 weeks at OPD Gynecology.

Case study 2: Thai female 22 years old 1st visit present with abdominal pain 1 day. PHI 1 day PTA abdominal pain generalize with vaginal bleeding no nausea and vomiting not diarrhea normal urine. Gravida 3 Para 1 Abort 1 (ectopic pregnancy) Labor 1 last 2 years. Refer to emergency room (ER) Kalasin hospital on 17 April 2022 12.02 p.m. At ER Pt. alert, abdominal pain with guading generalized tenderness observe vital sign(v/s) was show blood pressure 120/68 mmHg, pulse 86 beat per minute(bpm), respiratory rate (RR) 20 bpm and body temperature (BT) was 36.9, urine preg test (UPT) was positive, urine amphetamine was positive, Hct. was 28.4 % ultrasound was found rupture right tubal pregnancy free fluid in abdomen was positive estimate 500 ml. Shock was identified get to manage shock and set operation exploratory laparotomy with right salpingectomy with removal tubal pregnancy stat. In operation room finding uterus mild enlarged, adhesion between bladder and anterior lower part of uterus, normal both ovaries status post left salpingectomy and right tubal pregnancy estimate size 2x2 cm. with rupture hemoperitoneum (blood clot) estimate 500 ml., in operation vital sign was show BT 36.6  PR. 98-100 bpm. RR 20-22 bpm. (On ventilator) BP. 100/60 mmHg. Post operation good conscious no bleeding per surgical wound no complications sign of shock not found transfer to Gynecology ward for observe. At ward Pt. good conscious V/S BT 36.6-37.3 C PR. 90-102 bpm. RR 18-20 bpm BP100/58-111/62 mmHg, no constipation plan for discharge on 19 April 2022 rang of stay 3 day and follow up 4 weeks at OPD Gynecology.

In other health status was comparative via Gordon's functional health patterns between case study 1 and case study 2 was show on the (Table 1).

Table 1: Comparative Gordon's functional health patterns between case study 1 and case study 2.

Health pattern

Case study 1

Case study 2

Health Perception

Feeling severe abdominal pain  tired, vertigo dizziness, pallor low self-care not aware the problem was happening occurs during

Good perceive in health care, get to health providers when illness knowing that it will be an ectopic pregnancy

Health Management

pregnancy and want  to continue pregnancy

and has a worried when she knows  must surgery

Nutritional-Metabolic

Get diet on time, like to clean diet

Get diet not on time, like spicy,

Elimination

Normal excretion, no history of function

Normal excretion, no history of function

Activity-Exercise

Like to exercise every day, well ability to work

Self-care, so long time to exercise 1-2 time per month, well ability to work

Cognitive-Perceptual

Feeling confused and tire and vary vertigo

Good sensory and perceptual,  decision making by herself

Sleep-Rest

Sleep on time every day get from 10.00 pm – 06.00 am, average to sleep for 8 hrs., no slumberous on day early wake up.

Not sleep on time in every day, short time to sleep, not sleepy and late wake up in some day

Self-perception/Self concept

Serious about this illness and knowing about ectopic pregnancy now.

Know about this pregnancy and know that was ectopic pregnancy after health provider describe

Role-Relationship

Good relationship in family

Good relationship in family

Sexuality-Reproductive

Normal

Normal

Coping/Stress Tolerance

Serious about abortion because she and her husband want to had child

Serious about surgery but can accept and adaptation by herself

Value-Belief

The most valuable is parents and husband induce the mind

Believe this illness it impossible. Believe about sacred things, about sin and merit

The comparative in case study all with normal standard of ectopic pregnancy sign and management was show on table 2.

Table 2: Data comparative and analysis in ectopic pregnancy of 2 case study.

Comparative points

Case study 1

Case study 2

Cause or factor of ectopic pregnancy is caused and

In operation was finded left tubal pregnancy with rupture left site fimbria hemoperitoneum blood clot estimate 300 ml and normal look of right OV. and FT. normal looked of left OV

In operation was finded uterus mild enlarge, adhesion between bladder and anterior lower part of uterus. Normal of both OV. Right tubal preg with rupture hemoperitoneum blood clot estimate 500 ml.

Risk factors are as follows:

Formation of adhesion around the fallopian tubes and

narrowing caused by inflammation and infection in

Pelvic floor, postpartum and post-abortion infections

1 day ago present with abdominal pain mild tenderness at left lower quadrant, right lower quadrant, suprapublic, no

1 day ago present with abdominal pain found distention, generalized tenderness and guarding.

Endometriosis Appendicitis increases at least 3 times the risk

Symptoms/Signs

The most common symptoms are tenderness in the lower abdomen (percentage

(80-95) has rebound) shape pain or colicky severe pain and acute, may be pain on one side or all over, this symptom precedes to rupture of the egg inside. Some case who had with intra-abdominal bleeding may be refer pain to the shoulder or area in case .was rupture, it will rebound tenderness

Guarding may be rebound tenderness

 

Amenorrhea, nausea and vomiting

G2P1A1 (ectopic pregnancy) L1 last 1year and 3 month. LMP not sure 

G2P1A1(ectopic pregnancy) L1 last  7 year and LMP 1 march 2022 for 3 day 

Menstrual spotting

LMP uncertain date estimate time 2 weeks PTA.

LMP 1 march 2022 for 3 day

Shock was found estimate 33 % most common after rupture fallopian tube may be hypovolemic shock  have an effect to vital sing unstable, blood pressure drop, limited of pulse pressure, tachycardia if who have abdominal bleeding may be found orthostatic

Good conscious look sic mild pale conjunctival, normal S1S2 no murmur, equal breast sound abdominal tenderness at right lower quadrant, suprapubic, Left lower quadrant no guarding may be rebound. Vital sing BP 114/80 mmHg PR 68 bpm RR 20 bpm. UPT positive Hct.28%.

Alert  Glassgow coma score(GS) E4V5M6 not pale no jaundice normal S1S2 no murmur normal breast sound abdominal guarding generalize tender vital sign stable BP 120/68 mmHg PR 86 bpm RR 18 bpm Hct 28.4% UPT positive and Urine amphetamine was positive

Hypotension, distend Cul-du-sac and tenderness 

 

Vaginal bleeding not nausea and vomited

Diagnosis

Rupture ectopic pregnancy with anemia of acute blood loss

 Rupture right tubal pregnancy with anemia of acute blood loss with amphetamine use

Sign and symptom

Abdominal pain 1 week

Abdominal pain 1 day PTA  1 day PTA abdominal pain generalize tenderness with

Week Pre Time-Admit (PTA) abdominal pain some time not pain LMP 2 weeks ago (Uncertain date) menorrhea.was 2 day standard was 5 day and sometime blood clot abnormaly

Treatment

UPT positive beta HCG result 53,621 Hematocrit (Hct.) 26.1% U/S was seen empty uterus, rupture left tubal pregnancy free fluid estimate 500 ml. Shock was identified get to manage shock sign then set operation for exploratory laparotomy with left salpingectomy under general anesthesia. In operation room was found left

UPT was positive, urine amphetamine was positive, Hct. was 28.4 % ultrasound was found rupture right tubal pregnancy free fluid in abdomen was positive estimate 500 ml. Shock was identified get to manage shock and set operation exploratory laparotomy with right salpingectomy with removal tubal pregnancy stat.

Observation about

Level of serum ß-hCG decrease

No abnormality bleeding per vagina

Size of ectopic no over 1 cm.

None sign of Tubal Rupture

Medical injection withmethotrexate destroy ectopic

Mass until mass gradually disappear and show most of tubal normally and good impact in gestational age less than 6 weeks

Tubal pregnancy with rupture site at fimbria estimate of hemoperitoneum about 300 ml., normal looked of right ovary and fallopian tube, normal looked of left ovary

In operation room finding uterus mild enlarged, adhesion between bladder and anterior lower part of uterus, normal both ovaries status post left salpingectomy and right tubal pregnancy estimate size 2x2 cm. with rupture hemoperitoneum (blood clot) estimate 500 ml.

Surgery with procedure

Salpingostomy

Salpingotomy

Salpingectomy

 

Result

Case studied 1 was a married Thai woman 26 years old G2P0A1L0 last 3 years visit at Kalasin hospital present with abdominal pain Rt. lower quadrant investigate by ultrasound found ectopic pregnancy with rupture Rt. fallopian tube with shock go on fast tract surgery. In case studied 2 was Thai women 25 years old G3P2A0L2 post sterilize visit at Kalasin hospital present with lower abdominal pain left side with vaginal bleeding, urine pregnancy test was positive, ultrasound found ectopic pregnancy in left fallopian tube no rupture go on fast tract surgery on time. Nursing diagnosis obtained from evaluating the patients about the disease via evaluating the physical, spiritual and social aspects, it was found that there were problems that needed to be taken care, so a nursing care plan for both patients was developed and comparative as follows on table 3.

Table 3: Comparative nursing diagnosis, data support and nursing intervention of 2 case study.

Nursing Diagnosis

Nursing Intervention

Hypovolemic shock related to abdominal bleeding evidenced by ultrasound found ectopic pregnancy with rupture Rt. fallopian tube with blood loss

Assessment sign of shock, level of pain score, anemia and oxygen saturation (O2sat.) keep > 95%

*Found in case study 1,2

 

Acute pain related to tissue injury from rupture ectopic pregnancy evidenced by grimacing, expression of pain and abdominal guarding.

Nothing per oral (NPO)

Take intra venous fluid according to the treatment plan.

Oxygen mask with bag 6 liters per minute please take

Serum testing as blood group, complete blood count(CBC), electrolyte, hematocrit (Hct.) and hemoglobin (Hb.)

Retained foley catheter for observe urine’s color and urine’s volume keep>30 ml/hour

*Found in case study 1,2

 

Anxiety related to stress as evidenced by increased tension, apprehension, and expression of concern regarding upcoming surgery

Level of pain score assessment.

Take to analgesic according treatment plan

Semi-fowler’s position and bed rest

Observe v/s every 4 hours.

Training to deep breathing exercise

Setting the environment to relaxation.

Found in case study 1

 

Uncomfortable due to abdominal distension secondary to the operation received

Assess perceptions about disease and its causes

Relationship’s procreate and listen to felling of client

Empowerment and encourage

Pre operation information and consent in form

Found in case study 1,2

 

Grieving and loss due to loss of pregnancy evidenced by ectopic pregnancy and rupture fallopian tube

 

 

Assess level of pain score in abdomen and after surgery

Take to painkiller according treatment plan

Set position due to comfortable

Set environment for relaxation

Found in case study 1

 

6. Risk to complication after surgery evidence by post-operative salpingectomy

Providing Preoperative Instructions

Reducing Fear and Anxiety

Promoting Safety and Preventing Injury

Promoting Infection Control and Preventing Infections

Normalizing Body Temperature

Promoting Effective Breathing Pattern

Providing Care Post Anesthesia

Managing Pain Relief

Improving Circulation

Maintaining Skin Integrity

Initiating Postoperative Patient Education and Health Teachings

Administer Medications and Provide Pharmacologic Support

Found in case study 1,2

 

7. Risk for Infection related to tissue injury from surgery

Assess for the infection sign and causes of infection

Monitor and report any signs and symptoms of infection e.g   redness, swelling, increased pain, a purulent discharge from

Surgical wound, elevated temperature, monitor white blood cell (WBC) count.

Investigate the use of medications or treatment modalities that may cause immunosuppression.

Observe and report if client has a low-grade fever or new onset of confusion.

Determine factors that can reduce the effectiveness of hand hygiene.

Wash hands or perform hand hygiene before having contact with the client. Also, impart these duties to the client and their significant others and know the instances when to perform hand hygiene

Change dressing and bandages that are wet.

Take antibiotic drug according the treatment plan

In summary from table 3 found that health problem all of 2 cases was similar 1) Hypovolemic shock related to abdominal bleeding evidenced by ultrasound found ectopic pregnancy with rupture Rt. fallopian tube with blood loss 2) Acute pain related to tissue injury from rupture ectopic pregnancy evidenced by grimacing, expression of pain and abdominal guarding. 3. Uncomfortable due to abdominal distension secondary to the operation received. 4. Risk to complication after surgery evidence by post-operative salpingectomy and 5. Risk for Infection related to tissue injury from surgery. In addiction differentiate nursing diagnosis between case study 1 and case study 2 was 1. Anxiety related to stress as evidenced by increased tension, apprehension, and expression of concern regarding upcoming surgery 2. Grieving and loss due to loss of pregnancy evidenced by ectopic pregnancy and rupture fallopian tube that problem was found in case study 1 but case study 2 was none

The nursing outcome found that nursing care had been closely provided via expert nurses based on patient’s conditions to correct the shock. Finally, patient was safe from shock and other mentioned health problems. In addiction differentiate of nursing diagnosis between 1st and 2nd case were anxiety case studied 1 was done related illness and operative but case studied 2 none because her experience in two time of caesarians section and own sterilized. Nursing care had been closely provided via expert nurses based on patient’s conditions to correct the shock. Finally, patient was safe from shock and other mentioned health problems.

Conclusion

 Case study 1

 A married Thai woman 26 years old with a report of absence of 2-month period of menstrual visit at Kalasin hospital with lower abdominal pain, faint, good conscious. At Kalasin hospital, shock was worsening progressive treatment was on 0.9% Normal Saline Solution intravenous drip rate 120 ml/hrs. after that a patient’s clinical improved enough to tolerate the fast tract surgery for right partial salpingectomy was performed and found hemoperitoneal 1,000 ml. with ultimately, a patient’s conditions were dramatically recovered.  In summary, the patient’s health problems was 1st stage pre operated 1) actual hypovolemic shock (deficient fluid volume) due to massive blood loss in the abdomen secondary to ectopic pregnancy, 2) actual ineffective tissue perfusion related to progression of shock with decreased red blood cell to transport oxygen to tissues, 3) risk for fluid and electrolyte imbalance, 4) actual anxiety related to feelings that illness was worsening and is potentially life threatening (patient and significant others), 5) actual pain secondary to tissue injury, 6) actual anemia due to massive blood loss, and 7) actual alter in comfort due to abdominal distension secondary to the operation received. Nursing care had been closely provided based on patient’s conditions to correct the shock. Finally, Patient was safe from shock and those mentioned health problems.

Restrictions

  1. It have to short time for study due to limited of case in timing
  2. Because fast tract surgery it’s new innovation for surgery so it not clears for some process of system

Suggestions

In Nursing

Just to base on of development of clinical nursing practice guideline in ectopic pregnancy who undergo on fast tract surgery

To developmental

Result expands to other complex disease

To research study

Result expands for any research design

For Utilization

Result expands for setting policy in service in many divisions all of in Thailand and global

References

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  2. Nuchcharin Thongroch. Nursing care in ectopic Pregnancy: case study. Journal of Mahasarakham Hospital. 2022; 17: 128-
  3. Tawiwan Panthasri. Diagnosis in Ectopic pregnancy. Report in mid-year conference 2018. The royal thai college of obstetricians and gynecology. 2018; 11-18.
  4. Kitchpornteeranan M. Surgery in ectopic pregnancy. Report in mid-year conference 2018. The royal thai college of obstetricians and gynecology. 2018; 1-10.
  5. Elías Estrada JC, Huerta Sáenz IH, Campos Del Castillo KB, Coronado Arroyo JC, Flórez Mendoza A. Abdominal ectopic pregnancy: Report of two cases. Ver Peru Gibnecol Obstet. 2021; 67.
  6. Khetpanya T, Singhala K, Suwanimitr A. Outcome of pre-surgery preparation programe in fast tract surgery for patients with breast cancer at primary care unit. Research and Development health system journal. 2018; 11: 595-603.