The Effect of Fluid Therapy in Acute Post - operative Complications of Breast Cancer; Pain and Post - operative Nausea and Vomiting

1. Background

Post - operative nausea and vomiting (PONV) is nausea, retching, or vomiting occurring during the first 24 to 48 hours after surgery. PONV is the most common cause of patient dissatisfaction after anesthesia. In patient with pharmacological prophylaxis frequency of post - operative nausea and vomiting (PONV) is about 40% to 60% (1-3), and is about 70% to 80% in high risk patients without prophylaxis (4).

The mechanism of PONV is very complex and not completely understood. Brain structures involved in the pathophysiology of vomiting are located throughout the medulla oblongata of the brain - stem, not centralized in an anatomically defined ‘vomiting center’. Chemoreceptor trigger zone (CRTZ) is located at the fourth ventricle in the area postrema, and the nucleus tractus solitarius (NTS), in the area postrema and lower pons.

The use of volatile anaesthetics and opioid use increases the risk of PONV about two - fold, with risk increasing in a dose - dependent manner.

Low ASA physical status (I - II), history of migraine, and pre - operative anxiety are predictors of increased risk of PONV.

Body mass index and menstrual cycle phase seem to have no effect on the incidence of PONV.

The strongest predictive factors for PONV are female gender, non - smoking patient, past history of PONV, past history of motion sickness, and intra and post-operative use of opioids (5). Among these factors, female gender is the greatest risk factor (6). Considering that breast surgery due to breast cancer almost completely done in females, PONV is reported up to 68% during the first 24 hours after surgery (7). The prevention of this complication plays an important role in pre - operative management (1). Also, this unpleasant symptom may cause patient discomfort and dissatisfaction, delayed discharge, and perhaps unplanned hospital re - admissions (8). Sometimes in prolonged cases, it may lead to electrolytes imbalance, dehydration, bleeding, tention on sutures, airway compromise, aspiration pneumonia, emphysema and more medical charges due to prolonged hospital stay (9, 10).

Intravenous hydration has been shown to reduce PONV, but there is no agreement as to which type of fluid or how much is suitable for preventing this complication (11).

Many studies investigated pre - operative venous hydration effect on PONV for PONV prevention (12).

All in all, there is limited information regarding the effect of different intravascular fluid administration. So in this paper, we compared the effect of different ways of administration of pre - operative and intraoperative fluid on PONV in patients undergoing breast cancer surgery.

2. Methods

After the approval of the study by the research ethics committee (Semnan University of Medical Science, Semnan, Iran), all patients, who met the inclusion criteria, were informed about the study and filled the informed written consent.

Ethical code:

IR.SEMUMS.REC.1394.196, IRCT201602116481N8.

Patients with the following criteria were included in this study:

1. Patients who were willing and able to sign the patients’ informed consent form.

2. Patients between 18 to 50 years old.

3. Patients who were scheduled for breast cancer surgery.

4. Patients with American Society of Anesthesiologists (ASA) Class of I or II.

The exclusion criteria included patients with a history of psychological disorders, smokers or drug addicted patients, history of cardiovascular disorders or diabetes mellitus, surgery duration more than 2 hours, excessive per - operative blood loss which needed transfusion, history of renal disease, history of motion sickness disease, history of PONV, poor controlled hypertension, weight more than 100 kg, and every other situation which does not allow fluid therapy. This study was conducted at the Shohada - e - Tajrish Hospital, a central teaching hospital in Tehran, Iran. Patients were selected according to the inclusion and exclusion criteria.

A total of 105 patients were randomly classified into 3 groups (35 each) based on random digits table. All of the patients received 1.5 mL/kg normal saline before surgery; also, all patients received 1.5 mL/kg/h normal saline as maintenance fluid therapy and 2 mL/kg/h as third space.

All patients received 3 mL normal saline to replace each 1 mL blood loss. In the first group (routines), serum therapy was as mentioned above and no additional fluids were administered (N = 35). In the second group ( pre - operative serum therapy), the patients received 5 mL/kg of ringer lactate serum 60 to 90 minutes before surgery in addition to routine hydration .Finally, in the third group (Intra - operative hydration), the patients received 5 mL/kg of ringer lactate solution during surgery in addition to routine serum therapy.

In 1 hour after recovery discharge also 4, 8, and 24 hours after surgery, the severity of PONV and post - operative pain were assessed, using cortile questionnaire and visual analogue scale (VAS) respectively by someone who did not know the goals of study. Dosage of anti - emetic used for the patients was compared between groups. Anesthesia management was the same for all the patients: After primary hydration, they received 3 µg/kg Fentanyl, 0.02 mg/kg Midazolam, and 1.5 mg/kg Lidocaine as premedication, the induction was done, using 1.5 mg/kg propofol and 0.5 mg/kg atracurium and intubation was done with endotracheal tube of optimum size for each patient propofol was used as maintenance for all of the patients. Bispectral index was held in 40 to 60 range and patients received 6 liter combination of oxygen and air (50% of each). Ten minutes before the end of surgery, all patients received 4mg ondansetrone (iv infusion) and 1000 mg paracetamol (iv infusion) for PONV and post - operative pain prevention, respectively. Revisal of neuromuscular blockade was done with the administration of 0.06 mg/kg Neostigmine and 0.02 mg/kg Atropine at the end of anesthesia. The data were analyzed by SPSS software version 18.

3. Results

A total of 105 women (35 in each group) were evaluated in this study. There was no meaningful difference considering age, literacy, weight, and height of patient (P > 0.05). The duration of breast cancer was 6.71 ± 5, 5.17 ± 3.66, and 5.89 ± 3.38 years in routine, pre - operative, and intraoperative fluid therapy groups, respectively, showing no significant difference. Most of the patients were in stage 2 of breast cancer and 3.6 and 6 of them in routine, pre - operative and intraoperative groups had a history of chemotherapy or radiotherapy, respectively.

Pre - operative fasting time, pre - operative, and intraoperative routine serum therapy were also the same in 3 groups.

Intraoperative systolic and diastolic blood pressure, heart rate, respiratory rate, O₂ saturation, and hematocrit levels were not significantly different between the groups.

Although there were no difference in considering the duration of surgery, blood loss was significantly lower in intraoperative serum therapy group (P = 0.007).

Nausea, vomiting, and post - operative pain were significantly lower in those patients, who received excessive serum pre - operatively (P < 0.05) (Table 1).

Twelve patients (30% - 40%) in first group (routine serum therapy), 8 patients (22.9%) in the third group (intraoperative serum therapy) and only 1 patient (2.9%) in the second group received Metoclopramide and these differences were statistically significant (P = 0.008), 31.4%, 17.1%, and 8.6% of patients in 3 groups received Acetaminophen, respectively (P = 0.048).

4. Discussion

Post - operative nausea and vomiting (PONV) harmfully influence patient satisfaction. There are multiple different drugs and techniques used in the prevention of PONV.

Three classes of anti - emetic drugs are serotonin antagonists (e.g. ondansetron), corticosteroids (e.g. dexamethasone), and dopamine antagonists (e.g. droperidol). Three other serotonin antagonists, namely granisetron, dolasetron, and palonosetron have the same effect and side - effects.

The D2 receptor antagonist droperidol has a short plasma half - life and we should be given at the end of surgery.

Low dose dexamethasone is the same efficacy against PONV and post - surgical pain.

Neurokinin - 1 receptor antagonists are new class of anti - emetics that were originally developed and useful nausea and vomiting induced during chemotherapy.

Metoclopramide is a widely used D2 antagonist; 25 mg to 50 mg has similar efficacy compared with other anti - emetics; it is not useful at its regular dose (10 mg).

Transdermal scopolamine (a cholinergic drug) administered the night before or the day of surgery has also showed a 40% risk reduction in PONV, but increases visual disturbance three - fold.

If possible, use loco - regional anaesthesia instead of general an - aesthesia. If general anesthesia is required, total i.v. anesthesia with propofol and nitrogen reduces the incidence of PONV by 30%, making this intervention as effective as an anti - emetic drug.

Limiting the pre - operative administration of opioids decreases not only the risk of PONV but also hyperalgesia.

Obeying fasting strategies pre - operatively, patients are routinely hypovolemic in the operating room; so there are many patients experiencing the hypovolemic episodes, which increase the incidence of PONV. Therefore, sufficient hydration is one of the easiest strategies used in the prevention of PONV.

In this study, the effect of pre - operative, intraoperative, and routine hydration on PONV were compared.

It was observed that pre - operative hydration decreases nausea and vomiting more than intraoperative hydration; on the other hand, intraoperative hydration decreased PONV more than routine serum therapy and this difference was statistically significant. Several studies concluded that pre - operative intravenous fluids may be useful for the prophylaxis of PONV (13-15).

4.1. Conclusions

Pre - operative fluid administration with crystalloids caused lower incidence of PONV compared to routine hydration. It also reduced post - operative pain and risk of anti - emetic and analgesic administration.