The analgesic efficacy of nonsteroidal anti-inflammatory drugs and tramadol after transnasal surgery for pituitary adenomas was compared

Recently, Guo Xiaopeng et al.
of the Department of Neurosurgery of Peking Union Medical College Hospital designed a randomized, double-blind, non-inferiority clinical trial of postnasal analgesia in patients with pituitary tumors to evaluate the analgesic effects of NSAIDs and tramadol, and to compare the application of opioid remedial therapy; The results were published online in the November 2021 Journal of Neurosurgery
.

——Excerpt from the article chapter

【Ref: Guo X, et al.
J Neurosurg.
2021 Nov 26; 1-10.
doi: 10.
3171/2021.
8.
JNS211637.
[Epub ahead of print]】

Research background

Pituitary adenomas (PA) are common primary central nervous system tumors with an annual incidence of 4.
2 per 100,000 people
in the United States.

Endoscopic nasal approach surgery has little neurovascular damage and high total resection rate, so in most cases it replaces craniotomy; However, in patients with sensitive nasal mucosa, postoperative pain is serious
.

Opioids are effective analgesics, with side effects ranging from nausea and vomiting, respiratory depression and even addiction, so it is clinically recommended to choose a ladder analgesic, nonsteroidal anti-inflammatory drugs (NSAIDs) and a second-order analgesic, tramadol
.

Recently, Guo Xiaopeng et al.
of the Department of Neurosurgery of Peking Union Medical College Hospital designed a randomized, double-blind, non-inferiority clinical trial of postnasal analgesia in patients with pituitary tumors to evaluate the analgesic effects of NSAIDs and tramadol, and to compare the application of opioid remedial therapy; The results were published online in the November 2021 Journal of Neurosurgery
.

Research Methods

The study collected data on 202 patients with pituitary tumors who underperformed nasal surgery at Peking Union Medical College Hospital between November 1, 2020 and May 31, 2021; Among them, 101 cases were in the NSAIDs group, and 40 mg of parecoxib was given intravenously after surgery, followed by oral loxoprofen sodium 60 mg twice a day; The other group, tramadol group, was given tramadol injection 100 mg intramuscularly after surgery, followed by oral tramadol tablets 100 mg twice
a day.

Exclude patients with
rhinitis, sinusitis, or deviated nasal septum causing chronic nasal pain, history of peptic ulcers or bleeding, heart disease, liver failure, acute or chronic kidney disease, postoperative coronary bypass surgery, allergy or abuse of NSAIDs, and pregnancy.

Both groups of patients underwent visual analog scale (VAS) on the first three days after surgery to assess pain levels and complications
by visual analog scale (VAS) at 8 a.
m.
, 12 p.
m.
, 4 p.
m.
, 8 p.
m.
, and 12 p.
m.

If the VAS score > 6 for 4 hours, breakthrough pain is considered and piperidine 50 mg is given, intramuscularly; Severe nausea and vomiting are given ondansetron 4 mg intravenously; Severe dizziness is given oral sensitization to make lang 6 mg; Gastric ulcers and gastrointestinal bleeding patients immediately stop taking painkillers and intravenously inject esomeprazole 40mg
.

Results of the study

The primary endpoints of this clinical trial showed that the mean VAS score in the NSAIDs group at 24 hours after surgery was significantly lower than that in the tramadol group (2.
6±1.
8:3.
5±2.
1; 95% CI, -1.
5 to -0.
4; non-inferior P<0.
001, superior P<0.
001).
<b10>
Secondary study endpoints showed that the mean VAS score for pain at 48 hours postoperative was significantly lower in the NSAIDs group than in the tramadol group (2.
2±1.
6:3.
1±1.
8; 95% CI, -1.
3 to -0.
4; non-inferior P<0.
001, superior P<0.
001).
<b12>
The mean VAS score of pain at 72 hours postoperative 72 hours in the NSAIDs group was lower than that in the tramadol group (1.
8±1.
4: 2.
6± 1.
6; 95% CI, -1.
2 to -0.
3; non-inferior P<0.
001, superior P<0.
001).
<b14>
Postoperative nausea in the NSAIDs group (39.
6%: 61.
4%; 95% CI, -35.
3% to -8.
3%; Non-inferior P<0.
001, superior P=0.
002), vomiting (3.
0%: 42.
6%; 95% CI, -49.
8% to -29.
4%; Non-inferior P<0.
001, superior P<0.
001) and dizziness (12.
9%: 47.
5%; 95% CI, -46.
3% to -22.
9%; The proportion of patients with non-inferior P<0.
001 and superior P<0.
001) was significantly smaller than that of tramadol group, but the proportion of patients with postoperative gastric discomfort in the NSAIDs group was significantly higher than that in tramadol group (9.
9%: 2.
0%; 95%CI，1.
5%-14.
3%； Non-inferior P=0.
447, superior P=0.
017).
<b16>
The proportion of patients applying piperidine for breakthrough pain after surgery in the NSAIDs group was significantly lower than in the tramadol group (4.
0%: 15.
8%; 95% CI, -19.
9% to -3.
7%; Non-inferior P<0.
001, superior P=0.
005).
<b18>
VAS values in both groups of patients with pituitary adenoma decreased significantly and continuously within 72 hours after surgery; Of the 15 time points, the VAS values of the NSAIDs group were significantly lower than those in the tramadol group
.

Post-mortem analysis showed that among the three subgroups with hypopituitary hormone and no hypopituitary hormone before surgery, patients with acromegaly and acrificial hypertrophy, and cerebrospinal fluid leakage and no cerebrospinal fluid leakage during surgery, the trend of NSAIDs and tramadol group in the main study endpoint and secondary study endpoint was basically the same; Patients with preoperative headache have higher postoperative VAS scores (P<0.
05) than those who do not have headaches<b112>.

Conclusion of the study

This study is the first clinical trial to compare the effects of NSAIDs versus tramadol analgesia in patients with pituitary tumors after nasal surgery, and the results show that compared with the second-order analgesic drug tramadol, the first-order analgesic NSAIDs significantly reduce acute pain after nasal surgery, causing a low incidence of adverse events, and fewer
patients requiring remedial addition of opioids.