Atomized Intranasal Vs Intravenous Ketorolac in Acute Renal Colic Pain Management.

Research objectives and hypothesis:

The aim of this study is to compare the analgesic effects of intranasal Ketorolac tromethamine versus intravenous Ketorolac tromethamine in adult patients with moderate to severe renal colic seen at the Emergency Department at Sultan Qaboos University Hospital.

Study design:

Prospective double-blinded randomized clinical trial in adults (from age 18 to 64 years) who presents to the emergency department (ED) at Sultan Qaboos University Hospital with moderate to severe acute flank pain suggestive of renal colic (visual analog scale 7 or more). Written consent will be obtained from the patient. Eligible subjects will be enrolled (see section 5).

Control Group Will receive 30 mg intravenous ketorolac in 10 ml syringe + 1 ml Normal Saline 9% using the intranasal device (0.5 ml in each nostril).

Intervention Group Will receive 30 mg intranasal ketorolac in 1 ml intranasal device (0.5 ml in each nostril) + 10 ml Intravenous Normal Saline 9%.

Primary endpoint:

Analgesic effects of Intranasal Ketorolac on the visual analog scale (VAS). Change in visual analog scale after receiving intranasal ketorolac. 0 (no pain) - 10 (worst possible pain).

Secondary endpoint:

• Adverse Event/Side Effects.
• Safety assessed by reporting all adverse events.
• The need of rescue pain medications.
• Time to discharge.
• Recurrent visit within 24 hours.

Sample size:

after 1 hour follow-up, 146 patient will be needed ( 73 on each arm) to have 90% power to detect a difference of a 0.7 of the response of visual analog scale score ( which usually ranges between 0 and 10 ) between the groups (5.3 vs 4.6) at the 5% alpha (significance) level. Because of missing data and losses to follow-up, an additional 54 subjects will be needed (100 in each arm) for a total of 200 subjects (study sample). A P-value <0.5. Level of significance to be used.

Study Procedures:

1. Present to the Clinical Site Adult subjects ages 18 to 64 years with a classical presentation of acute renal colic being seen in the emergency department may be eligible for this study. Clinical sign and symptoms

• Severe flank pain radiating inferiorly and anteriorly with or without:
• Nausea and vomiting.
• Urinary symptoms.
• Previous history of renal colic.

1. Eligibility Assessments Inclusion and exclusion criteria will be check.
2. Informed Consent Potentially eligible participants will be identified by their treating clinicians. Written informed consent to participate in this study will follow a process of information exchange between clinicians and potential participants.
3. Study Pain Assessments Three pain assessments will be done based on VAS-Pain at:

• 0 minutes
• 30 minutes
• 60 minutes Pain scores will be recorded and documented before the administration of medication for a baseline pain assessment and at specified intervals after the administration. Post-treatment pain scores will be recorded at 0, 30 and 60 minutes. Pain assessments will be by the Visual Analog Scale for Pain. It is usually presented as a 10cm horizontal line on which the patient's pain intensity is represented by a point between the extremes of "no pain at all" and "worst pain imaginable." All patients must have a minimum of two pain scores. If rescue medications were given, a VAS-Pain will be obtained immediately prior to treatment.

1. Standard-of-Care Procedures: Pain Management Patients may receive additional medications as part of their emergency department treatment including additional pain medications, such as opioids. Any additional medications administered will be recorded. The need for additional medications (including the drug administered, the dose, the time, and the route of administration) will be recorded.
2. Safety Assessments All adverse events will be documented on an adverse event case log. Serious adverse events should be immediately reported to the primary investigator. Any serious, adverse event will be reported immediately to the Institutional Review Board.

Adverse Events is considered serious if it causes a threat to the patient's life or functioning. The U.S. Food and Drug Administration (FDA) defines a serious adverse event (SAE) as any untoward medical occurrence that:

• Results in death.
• Life-threatening (places the patient at risk of death).
• Requires hospitalization or prolongs an existing hospitalization.
• Causes persistent or significant disability or incapacity.
• Requires medical intervention to prevent one of the above outcomes.

RISKS AND BENEFITS Ketorolac has been proven effective for pain relief, especially for certain types of pain, such as musculoskeletal pain, headaches and the pain from renal colic. Inappropriate patients, ketorolac is a relatively safe drug for the treatment of pain. Side effects and complications, such as gastrointestinal complaints (e.g. abdominal pain, dyspepsia, GI bleeding) and renal dysfunction (elevation of the blood urea nitrogen and creatinine) have been reported but with appropriate patient's selection are uncommon or rare. The use of NSAIDS including ketorolac is not recommended in patients with active peptic ulcer disease, renal disease or at risk for renal failure due to volume depletion, cerebrovascular bleeding, hemorrhagic disorders, or those with a high risk of bleeding. With an appropriate patient selection, ketorolac can be a safe and effective medication for the relief of pain. The drug used in this study has a very low risk of developing any complications. However, during visits patients will be monitored for any complications and all adverse effects if any will be reported. With the proposed hypothesis, intranasal has the potential to reduce opioid use in the ED, provides fast, needleless and easy methods to apply. It will decrease the waiting time, cannulation and unnecessary blood investigations in patients with a classic presentation of acute renal colic.