Post-tonsillectomy hemorrhage and pain are the major complications of tonsillectomy, the optimal modality for achieving hemostasis remains unclear. According to our results, both hydrogen peroxide and adrenaline can help to reduce intraoperative blood loss, moreover, the intraoperative blood loss and the median operation time were significantly lower in the hydrogen peroxide group than in the adrenaline group. To our best knowledge, this is the first study to compare between hydrogen peroxide and adrenaline as hemostatic agents for tonsillectomy.
Unlike other studies that divided the patients into two groups, the distinctive characteristic of our study was that we focused on the same subjects; all patients served as their own control because hydrogen peroxide and adrenaline were applied to the opposing sides of the tonsillar fossa. Therefore, confounding factors such as underlying disease, age, sex, and tonsil size can be excluded. A few outliers might cause a disproportionate effect on statistical results because of the small amount of intraoperative blood loss in tonsillectomy. For example, the influence of surgeon handedness in tonsillectomy has not been examined in previous reports. To eliminate differences due to handedness, we compared the operation time and intraoperative blood loss on each side and further analyzed by type of agent (hydrogen peroxide and adrenaline) (Table 4 and Table 5). Our results revealed that hand preference did not influence overall outcomes based on operation time and blood loss as evidenced by the no significant differences between the two groups.
Table 4
Intergroup correlation of operation time, hemostasis time, and blood loss by side in the hydrogen peroxide group
Variables
|
Left (n = 30)
|
Right (n = 30)
|
p-value
|
Operation time (min)
|
9.72 ± 3.99
|
8.43 ± 3.74
|
0.201
|
Hemostasis time (min)
|
3.56 ± 2.53
|
3.65 ± 2.50
|
0.891
|
Blood loss (ml)
|
10.62 ± 4.60
|
9.96 ± 4.91
|
0.589
|
The independent T test is used for continuous variables. |
*p < 0.05 |
Table 5
Intergroup correlation of operation time, hemostasis time, and blood loss by side in the adrenaline group
Variables
|
Left (n = 30)
|
Right (n = 30)
|
p-value
|
Operation time (min)
|
7.99 ± 3.98
|
8.36 ± 3.29
|
0.696
|
Hemostasis time (min)
|
4.51 ± 3.79
|
4.12 ± 3.45
|
0.674
|
Blood loss (ml)
|
14.48 ± 7.18
|
12.64 ± 5.33
|
0.263
|
The independent T test is performed for continuous variables. |
*p < 0.05 |
A 2017 meta-analysis revealed that the application of local anesthetic either by infiltration or topical method could provide a modest reduction in post-tonsillectomy pain and hemorrhage12. The meta-analysis concluded that preoperative local anesthetic injection is a valuable method for decreasing blood loss and surgical time. Another meta-analysis suggested that topical local anesthetics on swabs provide similar analgesic effects as preoperative infiltration13. Previous studies showed that the general operation time by blunt dissection in tonsillectomy was 24.6–29.1 min.14,15 Adopting the above-mentioned strategies, including preoperative local anesthetic injection and postoperative topical application of hemostatic agents, reduced the mean operation time to 9.99–13.87 min in our study.
Electrocauterization for hemostasis can significantly decrease the operation time and intraoperative blood loss; however, it can also increase postoperative pain16,17. Further, it also results in excessive eschar on the tonsillar fossa, which may cause secondary bleeding3 and infection. In addition, time to wound healing and return to full diet is longer in patients undergoing bipolar cauterization hemostasis18.
In our study, the intraoperative blood loss was small (median volume < 15 ml) in both hydrogen peroxide and adrenaline groups. Topical hemostatic agents that have the benefit of rapid onset, easy accessibility, cost effectiveness, and analgesic effect are highly beneficial. We performed blunt dissection and applied topical hemostatic agents. Topical application of a hemostatic agent can treat all potential bleeding sites, not only focusing on an active bleeding area, but also on hard-to-access bleeding areas, such as the low pole of the tonsil. Thus, a topical hemostatic agent may be a feasible method to control hemorrhage. Hemostasis with the compression of a cotton ball may also cause lower postoperative pain than bipolar cauterization and ligation19. Topical hemostatic agents can also prevent sloughing of the eschar and help control mucosal bleeding across surface areas. No secondary bleeding after tonsillectomy occurred in the present study.
Hydrogen peroxide is widely used for wound irrigation owing to its hemostatic and antimicrobial effects. Chang et al. and Al-Abbasi et al. reported that the use of hydrogen peroxide significantly reduced the operation time in tonsillectomy by 35% and 31%, respectively5,20. In our study, hydrogen peroxide better reduced the operation time by 14.9% and achieved a better hemostatic effect than adrenaline. The decreased operation time in the hydrogen peroxide group could be due to the large extent to relatively short hemostasis time, in line with previous findings5,20.
For intraoperative blood loss, the median volume was significant lower in the hydrogen peroxide group than in the adrenaline group. We found that both hydrogen peroxide and adrenaline could decrease intraoperative hemorrhage. However, although the effect size of 3.88 ml of intraoperative blood loss may be significantly different, this little change may not have clinical significance. In addition, we also found that the mucosa and soft tissue turned white after hydrogen peroxide was pressed tightly. The chemical burns and bitter taste of hydrogen peroxide might explain the higher 24-hour postoperative pain score in the hydrogen peroxide group (4.98 ± 1.94) than in the adrenaline group (4.27 ± 1.97).
There are three main applications of hydrogen peroxide: antiseptic, hemostasis, and wound healing. Reactive oxygen species (ROS) defend the host from invading microbes by damaging microbial DNA. When hydrogen peroxide is degraded, reactive oxygen species are released, causing DNA strand breakage by DNA oxidization21. ROS induce interferon activation and result in an antiviral state, which limits viral replication. ROS may help promote cytokine production, autophagy, and granuloma formation, resulting in an antimycobacterial state. By decreasing the colonization of bacteria and viruses, the severity of infection and pain can be reduced.
In addition to the antiseptic benefit, we also found a decrease in operation time. Further analysis in the decreased operation time in the hydrogen peroxide group showed that the “bubble effect” due to oxidation in the early stage rapidly turned the bleeding area to white. This helped the surgeon to easily localize the bleeding source requiring cauterization and clarify the visual field. It also shortened the operation time. Applying hydrogen peroxide to the wound at the late stage can kill fibroblasts and promote re-epithelialization22. Hydrogen peroxide facilitates hemostasis through several mechanisms, including platelet aggregation, stimulation of platelet-derived growth factor activation, and regulation of the contractility and barrier function of endothelial cells23.
There are numerous theories regarding the hemostatic effects of hydrogen peroxide, including thermal injury of the vascular ends, oxygen embolization of vessels, and reactive vascular spasms24. More recently, it has been suggested that thrombolytic hyperactivity and thrombus formation can trigger hemostatic effects24. In addition, when catalase in red blood cells reacts with hydrogen peroxide, the chemical reaction induces the release of oxygen and heat, helping the surgeon to localize the bleeding site.
Currently, hydrogen peroxide is used clinically not only as a hemostatic and antiseptic agent, but also as a wound healing agent23. Hydrogen peroxide may help to clear pathogen debris and promote the cytokine secretion, helping tissue regeneration25. In our study, 3% hydrogen peroxide appeared to have no negative effect on wound healing. However, it should be noted that hydrogen peroxide carries a risk of cardiac arrest and stroke due to oxygen embolism formation26. The application time should be limited to prevent tissue damage and limit pain. Collectively, these findings support that 3% hydrogen peroxide is a safe and effective agent for intraoperative hemostasis and wound cleaning.
Hatton et al. reported that topical adrenaline is an effective hemostatic agent in tonsillectomy11. The application of bismuth subgallate and adrenaline paste to the tonsillar fossae reduced the operating time by 23% and blood loss by 21%27. Epinephrine, a platelet-stimulating agent, can cause aggregation of human platelets through alpha-adrenergic mechanisms28. In this study, we found that the topical use of adrenaline is mildly inferior to hydrogen peroxide with respect to hemostatic function. The vasoconstriction effect of adrenaline on arterioles, capillaries, and venules helps to delay intraoperative bleeding initially. However, post-tonsillectomy bleeding may result from a blood vessel that initially spasms and later resumes bleeding if hemostasis is not complete. Importantly, adrenaline takes longer to work in these cases. In the current study, the operation time and intraoperative blood loss were lower at 14.9% and 38.8% (3.88 cc) in the hydrogen peroxide group than in the adrenaline group. However, adrenaline was more effective for postoperative pain control in the first 24 hours, but the pain scores were similar at 48 hours postoperatively.
We combined lidocaine and adrenaline in this study because lidocaine could stabilize the neural membrane by inhibiting voltage-gated sodium channels, resulting in suppression of impulse conduction, affecting local anesthetic action. To prevent systemic circulation and adverse effects of as central nervous system toxicity, tachycardia, convulsion, respiratory obstruction29, and vocal palsy30, adrenaline was applied topically. The vasoconstrictor property of adrenaline prolongs anesthesia activity and minimizes the risk of systemic circulation. By stimulating α-adrenergic receptors on the neural vasculature, combining adrenaline with lidocaine can lower local blood flow, slow clearance of lidocaine, and extend the duration of peripheral nerve block action. However, although rare, toxicity at high doses of lidocaine can influence cardiovascular and central nervous system function in a concentration-dependent manner. This study has some limitations. The number of subjects enrolled in our study was too small to draw a definite conclusion. Previous studies measured pain before and after the administration of supplemental analgesia; however, there may still have been some residual analgesic effect on subsequent measurements in the early period. Meanwhile, we assessed the pain score at 24 h postoperatively when the anesthetic effect may have little residual activity. Furthermore, we found that it was difficult for some patients to precisely discriminate the exact pain score on each side, possibly resulting in a bias. Further studies should investigate the effects of hemostatic agents over a longer duration with a larger set of participants.
The topical application of hydrogen peroxide is beneficial for reducing the operation time and intraoperative blood loss with minor complications in tonsillectomy. Thus, hydrogen peroxide can be used as a routine topical hemostatic agent in tonsillectomy. Meanwhile, topical application of adrenaline provides significant pain relief on the first day.