Supplemental oxygen is not required in trauma patients treated with IV opiates

Supplemental Oxygen Is Not Required in Trauma Patients Treated With IV Opiates LEENA H. MILDH, MD,* ANNELI PIILONEN, MD,† AND OLLI A. KIRVELA¨, MD, PHD The risk of respiratory depression can prevent the proper use of opioids in trauma patients and lead to use of supplemental oxygen. However, high FiO2 might contribute to atelectasis formation and consequently to relative hypoxia. Supplemental oxygen also can cause a risk of fire. In a randomized, controlled study we evaluated the need and effects of supplemental oxygen in 13 patients with extremity trauma who were treated pain-free with an intravenous opioid, oxycodone (dose range 6.75-13.6 mg). After opioid injection, 7 patients received 40% supplemental oxygen and 6 were breathing room air. Pulse oxygen saturation (SpO2), arterial blood gases, and hemodynamic parameters were monitored for 30 minutes. Atelectasis formation was evaluated with a computed tomography scan. No hypoxia, hypoventilation, or significant atelectasis formation was detected in any of the patients. Accordingly, routinely given supplemental oxygen was not considered necessary in these patients because no complications were seen. (Am J Emerg Med 2003;21:35-38. Copyright 2003, Elsevier Science (USA). All rights reserved.)

Because of the risk of hypoxia, supplemental oxygen is often recommended for patients treated with respiratory depressant drugs such as opioids,1,2 which are the standard treatment for trauma-induced pain in the early acute period.3,4 Supplemental oxygen is thus widely used routinely during transportation and in EDs when opioids are given to trauma patients. Use of an oxygen mask, however, causes some concerns. In recent studies increased atelectasis formation has been reported when respiratory depressant drugs are used with increased inspiratory oxygen content.5,6 Therefore, the use of routine supplemental oxygen can be potentially harmful for patients treated with opioids. An important aspect with supplemental oxygen is safety. It can increase the risk of fire during transportation and in the ED when electrical devices are being used near the oxygen mask.7,9 In crisis situations when several patients are simultaneously being transported or admitted to the ED, delivering oxygen to all patients can become difficult and the risk of fire can further increase. Most of the studies focusing on opioid-induced respiratory depression have been performed in a postoperative setting where the residual effects of

From the *Departments of Anesthesia and Intensive Care Medicine and †Radiology, Helsinki University Hospital, Helsinki, Finland. Manuscript received and accepted March 9, 2002. This study was financially supported by the Scientific Advisory Board for Defense, Finland (grant no. Mdd568/00). Address reprint requests to Olli A. Kirvela¨, MD, PhD, Director, Associate Professor Department of Anesthesia and Intensive Care Medicine, Helsinki University Hospital P.O. Box 226 FIN-00029 Helsinki, Finland, E-mail: olli.kirvela@hus.fi Key Words: Opioids, supplemental oxygen, oxycodone, respiration, trauma. Copyright 2003, Elsevier Science (USA). All rights reserved. 0735-6757/03/2101-0007$35.00/0 doi:10.1053/ajem.2003.50007

general anesthetics can interfere with the effects of opioids. This data might not be applicable to trauma patients. Accordingly, the routine of giving supplemental oxygen might need to be reconsidered in patients with otherwise uncompromised respiratory function. The aim of this study was to evaluate the effects and need of supplemental oxygen in opioid-treated normovolemic patients with extremity trauma. MATERIALS AND METHODS Patients This study was approved by the local ethics committee and written informed consent was obtained from all participants before entering the study. The study was performed in the ED of a tertiary care trauma center of a university hospital over a period of 6 months. Criteria for entering the study were 1) acute trauma of the upper or lower extremities, and 2) severe pain, as assessed by a verbal rating scale (VRS, 0 ⫽ no pain; 1 ⫽ mild; 2 ⫽ moderate; 3 ⫽ severe; 4 ⫽ unbearable). Patients with the following characteristics were excluded from the study: (1) head, thoracic, or abdominal trauma, (2) hypovolemia, (3) severe obesity, (4) age under 15 or over 60, (5) chronic disease with medication, and (6) intoxication of any kind. Study Protocol The study was initiated on the patient’s arrival to the ED. During transport to the hospital only alfentanil in 0.25-to 0.5-mg increments was allowed for pain relief to meet the study criteria. After signing the informed consent form, the patients were enrolled in the study. Their upper arm vein was cannulated, if not done earlier, and an arterial catheter was inserted into the radial artery for blood sampling and blood pressure measurements. Pulse oxygen saturation probe was placed on a finger, or in the case of hand injury, on a toe. Plethysmographic belts were wrapped around the chest and abdomen for respiratory measurements. The baseline values for all parameters were recorded. The patients were then randomized to breathe either normal room air (RA) or 40% oxygen through a face mask (O). The first intravenous dose of 0.08 mg/kg oxycodone, a morphine-like ␮-agonist,10 was given to the patients by the investigator. In case of ongoing pain, additional doses of 0.04 mg/kg oxycodone were given 5 and 10 minutes after the first dose until the patient reported no pain at rest. After 30 minutes the last values for the study were recorded. The patients were then transferred to the radiology department, where a computed tomography (CT) scan of the lungs was performed. The 35

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inspired oxygen fraction selected for the patient by randomization was held until the end of the CT scan. Assessment Methods Arterial samples were drawn for measurements of oxygen tension (PaO2), carbon dioxide tension (PaCO2), as well as base excess (BE) and pH. The sampling points were at baseline (BL) 5 minutes after the first drug injection (5), 10 minutes after the first drug injection and 5 minutes after the optional second dose (10), and 30 minutes after the first drug injection (30). Mean arterial blood pressure, electrocardiogram, and heart rate were recorded along with pulse oxygen saturation with a Cardiocap monitor (Datex-Ohmeda, Helsinki, Finland). Respiratory inductive plethysmography (Respitrace, NIMS, Miami Beach, FL) was used for the measurements of respiratory rate and changes in tidal volume.11 For safety reasons, it was also used as an apnea monitor. The change in tidal volume is reported as change from the baseline measurement, which is referred as 100%. Computed Tomography Scanning For the CT (GE HiSpeed) the subjects were supine with their arms above the head. A spiral CT of the lungs was performed at the end inspiration, the slice thickness being 10 cm. No contrast medium was used. All CT images were evaluated and atelectasis or other signs of hypoventilation were recorded as “yes” or “no.” Two CT scans from each patient were chosen for further analysis. The chosen scans were 6 cm (upper) and 2 cm (lower) above the diaphragm. A region of interest (ROI) was drawn in both lungs separately. This region excluded the outermost part of the lung to avoid partial volume effect. Also, the great vessels were excluded medially. A histogram of the distribution of pixel density was made in these ROI areas and lung density was defined in terms of Hounsfield units.12 A value above-500 Hounsfield units (HU) was considered a poorly treated lung. The calculations were carried out both on the right and left lung separately. Side effects were recorded throughout the study. Statistical Methods Comparisons between the study groups were performed using unpaired Student t-test. To test the significant time effect within the study groups, a repeated measurementlinear model was used. Statistical computing was performed using the SAS system for Windows (SAS Institute Inc., Cary, NC). A P-value of ⬍ .05 was considered significant. The values are presented as mean (standard deviation). RESULTS Thirteen patients were originally recruited to the study. The groups were well matched for age, sex, type of injury, mean time from injury to initiation of analgesia, and weight (Table 1). The types of injuries are described in Table 2. All patients reported satisfactory pain relief within 10 minutes from initiation of the study, and the amount of oxycodone given was 9 ⫾ 2 mg (range 0.13-0.03 mg/kg) and 10 ⫾ 2

TABLE 1. Demographic Data of the Patients (mean ⫾ standard deviation)

Age (y) Weight (kg) Time from injury to analgesia (min) Sex (M/F) Type of injury Upper extremity/lower extremity

RA

O

30 ⫾ 10 67 ⫾ 8 225 ⫾ 278 4/2

32 ⫾ 14 76 ⫾ 14 142 ⫾ 63 4/3

3/3

3/4

Abbreviations: RA, room air; O, 40% oxygen.

mg (range 0.14-0.02 mg/kg) in RA and O, respectively (not significant) [NS]. The slightly, nonsignificant longer initiation time in the RA group was because one patient who injured himself on a cruise ship was transferred 790 minutes later to the trauma center. PaO2 remained near baseline in the room air group, but in the oxygen group it increased well above baseline level P ⬍ .05 (Table 3). SpO2 as well as PaCO2 remained within normal limits in both groups (Table 3). Both BE and pH remained within normal limits and there was no difference between the groups at any of the measurement points. Respiratory rate decreased slightly but nonsignificantly in both groups during the study. In the O group the decrease was 19 ⫾ 4/min to 14 ⫾ 4/min at 5 minutes and 13 ⫾ 2/min at 30 minutes (NS). In the RA group the decrease was 17 ⫾ 4/min to 15 ⫾ 7/min at 5 minutes and 14 ⫾ 3/min at 30 minutes (NS). Vt decreased slightly in the O group from 100% to 80% in 5 minutes and to 90% at 10 minutes (NS), but returned to 104% at 30 minutes. In the RA group Vt remained at baseline, 104% at 5 and 10 minutes and 100% at 30 minutes. No clinically significant atelectasis was noted in either of the groups. Three of 6 patients in the O group and 4 of 6 patients in the RA group showed signs of minimal, clinically insignificant dorsal-dependent atelectasis. The Hus did not differ between the study groups in any of the measured areas and were well below the values indicative of atelectasis (Table 4). Mean arterial pressure decreased somewhat in both groups, from 97 ⫾ 12 to 87 ⫾ 10 mmHg in the O group and from 95 ⫾ 9 to 92 ⫾ 8 mmHg in the RA group during the study (NS). HR remained within baseline level in both groups, 67 ⫾ 8 bpm in the O group and 73 ⫾ 16 bpm in the RA group. The side effects noted were a transient loss of p-wave in the electrocardiogram of patient 6 and a transient feeling of nausea in patient 9. DISCUSSION The importance of pain treatment in trauma patients has been emphasized in recent publications.3,13,14 Injuries to both upper and lower extremities can cause severe pain, yet inadequate use of analgesics in patients with acute fractures appears to be common.15,16 Opioids should be the obvious choice because they are fast-acting and effective even in severe pain, and they relieve both emotional suffering as well as trauma-related stress responses.4 Unfortunately, opioids are often withheld or given in inadequate doses because

MILDH ET AL ■ OPIOIDS AND SUPPLEMENTAL OXYGEN

TABLE 2.

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Diagnosis of All Patients

Patient No.

Group

Diagnosis

1 2 3 4 5 6 7 8 9 10 11 12 13

O RA O O RA O RA RA O RA O RA O

Open tibial fracture Traumatic amputation of 2-4 fingers Open tibial fracture Complicated comminuted fracture of the forearm, humeral neck fracture, finger fracture Tibial shaft fracture, lateral malleolar fracture of the ankle Traumatic finger amputation, burn injury of the upper extremity Displaced comminuted fracture of the olecranon Complicated comminuted fracture of the distal tibia Laceration wound of the forearm Comminuted fracture of the humeral shaft Comminuted duplex fracture of the tibia, femoral shaft fracture Pilon fracture of the distal tibia Femoral shaft fracture, fracture of the lateral condyle of the tibia, fracture of the clavicula

Abbreviations: O, 40% oxygen; RA, room air.

of the fear of side effects, especially respiratory depression.4,15,17 In this study, pain was safely and effectively treated with intravenous opioids. No sign of hypoxia or hypoventilation was seen in any of the patients studied. The routine use of supplemental oxygen was of no clinical value. Even if supplemental oxygen had no adverse effects, the possible fire risks associated with its use make its routine use questionable. When supplemental oxygen is given through a face mask, relatively high flows, even up to 8-10 L/min, are often used. This creates an area around the patient’s head where the use of electrical devices can create a serious fire risk. Oxycodone was chosen as the study drug because of its pharmacologic properties. The potency of oxycodone resembles that of morphine. The equianalgesic dose ratio of oxycodone and morphine in postoperative pain varies from 1:118 to 2:3.19 The onset of analgesia is faster with oxycodone than with morphine and the hemodynamic effects of oxycodone are minimal compared with morphine.10 According to this, if morphine is used in the treatment of normovolemic trauma patients, at least similar if not higher doses could be used without fear of respiratory depression. Opioids decrease respiration by reducing the responsiveness of brainstem respiratory centers to carbon dioxide, as shown by depression of minute ventilation with decreased PaO2 and increased PaCO2.20 In this study, no clinically significant hypoventilation was seen in any of the patients TABLE 3.

treated pain-free with intravenous opioid. Intravenous oxycodone did not cause clinically significant changes in PaO2 and PaCO2 in patients breathing room air. Intravenous fentanyl has been shown to decrease PaO2 and increase PaCO2 when given to patients with multiple rib fractures.21 Before admission, our patients had normal respiratory function, which probably explains this discrepancy. Pain can cause hyperventilation, and slightly decreased PaCO2 values were seen in some of the patients before drug injections. Otherwise the PaCO2 levels were normal throughout the study. Also, no changes were seen in the acid-base balance of the patients. No sign of clinically significant atelectasis was seen in any of the patients studied. In previous studies atelectasis formation was seen in patients treated with respiratory depressant drugs while breathing oxygen-enriched air.5,6 Low lung volumes in conjunction with high FiO2 were associated with this phenomena. Increased atelectasis formation is seen already with 30% oxygen, but the atelectasis formation is greater with increasing oxygen concentration, being most evident with 100% oxygen.5,22 This is considered to be associated with decreased tidal volume. In this study, tidal volumes were not decreased considerably and the inspired oxygen concentration was chosen to be 40%, not higher. These factors can contribute to the fact that no atelectasis was seen in any of the patients. In the previous studies in which atelectasis was seen, it caused some degree of hyp-

Respiratory Variables (mean ⫽ standard deviation)

Variable SpO2(%) pO2(kPa) pCO2 (kPa)

Group

Baseline

5 Min

10 Min

30 Min

O RA O RA O RA

99 ⫾ 1 98 ⫾ 1 15.6 ⫾ 6.1 13.3 ⫾ 1.5 5.0 ⫾ 1.0 5.1 ⫾ 0.9

98 ⫾ 2 97 ⫾ 1 21.7 ⫾ 4.2†§ 11.7 ⫾ 1.0 5.6 ⫾ 0.6 5.5 ⫾ 0.6

98 ⫾ 1* 96 ⫾ 1*† 22.8 ⫾ 3.1‡§ 12.0 ⫾ 1.6 5.9 ⫾ 0.6 5.7 ⫾ 0.8

98 ⫾ 2 97 ⫾ 1 22.3 ⫾ 5.2†§ 12.5 ⫾ 1.1 5.9 ⫾ 0.6 5.7 ⫾ 0.4

Abbreviations: O, 40% oxygen; RA, room air; 5, 5 minutes after opioid injection; 10, 10 minutes after opioid injection; 30, 30 minutes after opioid injection. *P ⬍ .05. †P ⬍ .005. ‡P ⬍ .0005 difference between the groups. §P ⬍ .05 difference from baseline.

AMERICAN JOURNAL OF EMERGENCY MEDICINE ■ Volume 21, Number 1 ■ January 2003

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TABLE 4. The Hounsfield Units of Different Lung Regions (mean ⫽ standard deviation) Group

Right Upper

Right Lower

Left Upper

Left Lower

O RA

⫺820 ⫾ 30 ⫺830 ⫾ 39

⫺800 ⫾ 20 ⫺840 ⫾ 40

⫺820 ⫾ 0 ⫺830 ⫾ 40

⫺800 ⫾ 10 ⫺820 ⫾ 40

tively and safely treated with an intravenous opioid without respiratory depression or hemodynamic compromises. We could show no benefit of supplemental oxygen to these patients and, accordingly, its routine use cannot be recommended. REFERENCES

Abbreviations: O, 40% oxygen; RA, room air; Right upper, a slice of the right lung 6 cm above the diaphragm; Right lower, a slice of the right lung 2 cm above the diaphragm; Left upper, a slice of the left lung 6 cm above the diaphragm; Left lower, a slice of the left lung 2 cm above the diaphragm.

oxia despite the supplemental oxygen.5,22 All our patients breathing 40% oxygen had oxygenation values well above normal, supporting the conclusion of normal lung function. Opioid treatment slightly, although nonsignificantly, decreased mean arterial pressure, but did not affect heart rate. The baseline level of mean arterial pressure was high, probably the result of pain. The decrease in mean arterial pressure can thus be considered beneficial, even though the decrease was minimal. The patients were asked about pain on arrival to the ED and they were recruited according to the subjective feeling of pain (4 or 5 on the VRS). The amount of intravenous oxycodone needed to treat acute extremity trauma was fairly high, 9 ⫾ 2 mg and 10 ⫾ 2 mg in RA and O, respectively. These doses were administered within 5 to 10 minutes. The analgesia was sufficient enough to last at least until the end of the study period (30-60 min) when the CT scan was completed. Analgesia was introduced by one of the investigators standing next to the patient. This ensured a good level of analgesia would be reached in a short period of time. A titration of opioids is recommended in the treatment of acute pain.4 However, achieving a sufficient analgesia using small, incremental doses with several minute intervals can take a long time. The doses used in this study were safe to be injected in 5 to 10 minutes, and the analgesia lasted long enough to ensure radiologic interventions. One of the limitations of this study is the small sample size (13 patients). However, the two study groups were comparable and the results obtained from this study are uniform: no single hypoxic or hypercapnic period and no decrease in pulse oxygen saturation under normal limits. The power of this study was not sufficient enough to detect a change in mean arterial pressure or respiratory rate, which could be considered a sign of adequate pain relief. Furthermore, the results of this study are only applicable to normovolemic and previously healthy patients. Patients with considerable bleeding or chronic heart or lung disease would probably respond differently to these doses of opioids. Single extremity trauma can cause considerable pain regardless of the location of trauma. This pain can be effec-

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