EA is a known and not uncommon phenomenon that occurs during early postoperative awareness after general anesthesia. Patients who have post-traumatic stress disorder (PTSD) have shown higher incidence as well as more resistant symptoms of EA due to altered neurotransmitter system [5].
Trauma could be experienced and perceived differently [1]; with recent massive influential events such as the COVID-19 pandemic [27, 28] and wars around the world, specifically the Middle East [29, 30], it is more likely to expect PTSD. Accordingly, preparing a reliable anesthetic protocol would be crucial to ensuring smooth recovery and emergence [1]. Variable interventions were introduced pre-, intra-, and post-operatively to avoid EA in PTSD patients, with the less invasive, aversive, and lower harmful side effects being the most favorable [1, 5].
In the current study, we aimed to compare three different intervention techniques used for avoiding EA in PTSD patients undergoing gynecological laparoscopic surgery. The first strategy was applying preoperative relaxation techniques (deep breathing exercises and PMR); the second was administering intraoperative intravenous Ketamine injection; and the third was combining both previously mentioned strategies. All three intervention groups (1, 2, and 3) showed significantly lower HR 1-5 and HR IP to 24h than the control group 4. Group 1 (relaxation technique group) showed lower HR 1-5 and IP to 24h than the other two intervention groups. That could be attributed to the vagal stimulation of relaxation techniques on HR [31]. Percentage decrease of HR from the first intra-operative measurement (HR1) consistently till the 5th (HR5) was significantly lower in the three intervention groups compared to control.
In contrast, the percentage decrease from HR IP to 24h was higher in group 2 (intraoperative ketamine group); the higher HR IP could explain that in group 2 due to the effect of ketamine on increasing the HR (sympathomimetic effect) [32, 33] in addition to the stress of extubation and recovery from anesthesia. After 6 hours from the operation (HR 6h), the HR began to decrease gradually till HR 24h with fading of the ketamine effect [34], leading to a higher percentage decrease in this group. On the other hand, in group 3 (combined relaxation technique/intra-operative ketamine group), the relaxation techniques minimized the sympathomimetic effect of ketamine on HR IP, allowing the HR decrease to fall with fewer intervals till HR 24h, hence leading to smaller percentage decrease of HR IP-HR 24h.
Recently, non-pharmacological interventions have gained popularity, mainly because they yield effective results regarding smooth recovery, early ambulation, and hospital discharge at less cost [35, 36]. In light of these findings, Barabady et al. (2020) in Iran concluded that relaxation techniques based on deep breathing and muscle relaxation (Benson's deep relaxation) reduced heart rate and blood pressure and stabilized patients' respiration [35]. Likewise, Salah et al. (2022) in Egypt confirmed the efficacy of deep breathing exercises in pain reduction and hemodynamic stability (including heart rate and blood pressure) of patients during chest tube removal following cardiac surgery [37]. In agreement, Pardede et al. (2020) in Indonesia found that deep breath relaxation and lavender aromatherapy were effective7 in reducing preoperative anxiety, heart rate, and anticipated pain [14].
The findings of our study regarding the ketamine effect were supported by Demir et al. (2018) in Turkey, who proved the effectiveness of a sub-anesthetic dose of ketamine in reducing HR, blood pressure, pain, and EA [38]. Also consistent with our results, Andibirku et al. (2022) in Ethiopia reported a significant rise followed by a decrease in HR after 10 minutes in the ketamine group, which did not occur in the comparative group who received thiopental in addition to ketamine [39].
In the current work, the three intervention groups (1, 2, and 3) generally showed significantly lower MABP 1-5 and MABP IP to 24h than the control group 4. However, intra-operatively, MABP 1-5 percentage decrease showed no significant difference between the four groups. That could be due to the effect of other anesthetic drugs, which were given equally in all groups, including the control one, such as intravenous propofol administered during induction and inhalational isoflurane used for maintenance of anesthesia. Interestingly, only group 1 (relaxation technique group) MABP IP to 24h percentage decrease was statistically significant, while the other intervention groups, 2 (intraoperative ketamine group) and 3 (combined relaxation technique/intra-operative ketamine group), did not show a significant difference. As mentioned before, ketamine is a sympathomimetic drug, which causes vasoconstriction and hence higher blood pressure and, therefore, a smaller percentage decrease in MABP IP to 24h. On the other hand, relaxation techniques are parasympathomimetic and cause vasodilatation and vagal stimulation, which allowed a percentage decrease in MABP IP to 24h, especially when unopposed with ketamine (in group 1). At the same time, it was opposed to ketamine (in group 3).
Concordant results were reported by Barabady et al. (2020) in Iran [35] and Salah et al. (2022) in Egypt [37] concerning the relaxation techniques effect on the MABP in our study. In addition, Ali et al. (2022) in Iraq similarly concluded that the heart rate and mean atrial blood pressure were initially higher in the group of patients who received ketamine in addition to propofol than in the group with propofol alone. However, the difference was not statistically significant. Yet, the ketamine/propofol mixture was significantly better for maintaining hemodynamic stability for 30 minutes after induction [40].
The present study showed an increase in the pain scores (VAS) that occurred late in the intervention groups (1, 2, and 3) after VAS 6 because of the effect of relaxation exercises, ketamine, or both, which controlled the pain with their early application. The VAS in group 4 was higher immediately postoperative (since VAS 1) because the pain was not interfered with. That's to say, the first rescue analgesia was needed late post-operatively among the intervention groups (1, 2, and 3), while it was necessary from the start of the postoperative period in group 4.
Supportive findings were concluded by Baljon et al. (2022) in Saudi Arabia [41], who found breathing exercises to help lower VAS scores. However, they used breathing exercises combined with foot reflexology and massage (BRM) during labor. Salah et al. (2022) in Egypt [37] and Pardede et al. (2020) in Indonesia [14] also agreed on the effect of deep breathing on pain reduction after surgery, while Chaudhuri et al. (2020) in India proved that progressive muscle relaxation exercise was highly effective in reducing anxiety in painful conditions (such as coronary artery disease) [42].
The results of our study concerning the ketamine effect on the VAS score were consistent with the findings of Demir et al. (2018) in Turkey [38] and Han et (2022) in China, who confirmed the effectiveness of ketamine in decreasing postoperative VAS score, nausea, and vomiting and achieving better recovery from anesthesia [43].
In this study, participants in the intervention groups (1, 2, and 3) were significantly calmer, more cooperative, and less agitated than group 4. Cases in Group 1 were 85 times more likely to be non-agitated, those in Group 2 were 175 times more likely, and all of Group 3 were protected against agitation. Complete protection among group 3 cases could be due to the additive effect of parasympathetic stimulation of the relaxation techniques and the analgesic effect of ketamine.
No study measured the effect of relaxation techniques on EA specifically to our knowledge. However, lower anxiety and pain, as well as higher stability of patients who were offered relaxation techniques, are in favor of this conclusion. Likewise, Elsayed et al. (2020) in Egypt [44] found progressive muscle relaxation to be significantly effective in decreasing postoperative pain and improving the postoperative quality of patients' recovery after surgery.
The role of ketamine in decreasing the risk and symptoms of EA in our work was supported by the Yan et al. (2015) meta-analysis [45] and Demir et al. (2018) in Turkey [38]. Concomitantly, Lovestrand et al. (2017) in the USA [5] and Closson et al. (2024) in the USA recommended a sub-dose of ketamine early intraoperatively during the general anesthesia clinical practice guidelines for patients with PTSD [46].
Furthermore, the current work findings showed that postoperative nausea and hemodynamic instability were significantly less in all three intervention groups compared to the control group with no statistically significant intergroup difference, which could also be explained by the equal effectiveness of both preoperative relaxation techniques and early intra-operative intravenous ketamine in stabilizing the patient post-operatively (regarding nausea and hemodynamics) without a statistically significant effect on the recovery time. Concordantly, Ibrahim et al. (2020) in Egypt [47] and Dewi et al. (2021) in Indonesia [48] concluded that postoperative nausea and vomiting significantly decreased after diaphragmatic (deep) breathing performance. The results of Yan et al. (2015) meta-analysis [45], Demir et al. (2018) in Turkey [38], and Han et al. (2022) in China [43] were also in agreement with our findings regarding the ketamine effectiveness in these aspects.
As observed from the results of our study, the effect of intra-operative low-dose Ketamine injection in decreasing the incidence of EA was confirmed in patients with PTSD. Preoperative relaxation techniques (breathing exercises and PMR) had similar effects on lowering HR, MABP, VAS score, and EA without much privilege of their combination. Relaxation techniques could reduce costs by sparing anesthetic and analgesic drugs and minimizing hospitalization time. Accordingly, we suggest that relaxation techniques (namely, breathing exercises and PMR) could be included in the preoperative preparation protocol to decrease the risk and/or symptoms of EA, particularly among patients who test positive for PTSD.
