The first study on opioids for intrathecal anaesthesia was carried out by Racoviceanu-Pitesti, a Romanian surgeon, who presented his experience in Paris in 1901 (7). Since then opioids have become the most popular adjuvants for intrathecal anaesthetic administration (8) and are widely used as a single dose to provide post-operative analgesia (4). The beneficial analgesic effects of ITM administration have become well recognised (9–15) and is considered by some to be the gold standard for single-dose neuraxial opioid due to its postoperative analgesic efficacy and prolonged duration of action (16). ITM provides decreased pain intensity and for 24 hours post-operatively with decreased adjuvant analgesic requirements, being particularly evident after abdominal surgery (17). It has also previously been proven as superior to opioid based patient-controlled analgesia (PCA) as a form of post-operative pain relief (12, 18). However, irrespective of its superiority, other authors argue that an unfavourable risk:benefit profile makes the intrathecal application of morphine an undesirable technique (19). The possibility of reduced respiratory drive with accompanying hypoventilation, central apnoea and desaturation is a known side effect (20), especially when higher doses of ITM (> 300mcg) are used (21).
Even with numerous studies exhibiting the longevity of ITM for post-surgical analgesia, there remains a lack of consensus or evidence to create a linear dose response relationship for either the beneficial analgesic effects, or the harmful side effects of ITM (17). The magnitude of analgesia or the optimal dose of ITM has remained elusive with several studies failing to reach consensus ((14, 22–26)). A ceiling of analgesic effect has been suggested above which the risk benefit ratio begins to become unfavourable. Rathmell et al (21) in their review of over 1400 articles concluded that the analgesic effects of ITM become overshadowed by the side effect profile above a dose of 300mcg, and this has been shown specifically in relation to the general surgical cohort (17). In a large meta-analysis of studies on spinal anaesthesia it was shown that ITM doses of < 300mcg were not associated with higher rates of respiratory depression than placebo (5). Giovannelli et al performed a meta-analysis on studies on spinal anaesthesia and ITM administration, they found no significant increase in the incidence of respiratory depression in cohorts who received < 300mcg ITM versus sham (4). In addition to this, Koning et al in 2018 also showed, in a cohort of 56 patients who underwent Laparoscopic Segmental Colonic resection, that application of 300mcg ITM was associated with a significant decrease in opioid use and lower pain scores on postoperative day one and that there were no differences in adverse events, time to mobilization, fluid administration, or patient satisfaction (13). As well as this they showed that median time to discharge was significantly decreased in the ITM group.
This dose recommendation has been replicated in the orthopaedic setting with 200-300mcg ITM being recommended for total knee replacement by Hassett et al (27). Evidence would appear to strengthen the case for the above aforementioned dose of 300mcg intrathecal morphine as a safe and effective dose with an acceptable side effect profile and as such most probably the optimum dose with regards to the risk:benefit ratio of ITM administration.
However, in one case study, in which a patient was inadvertently administered 4000mcg of ITM, the patient was monitored for 180 minutes after administration and a respiratory rate between 12–16 breaths per minute was noted. This patient was subsequently treated with naloxone after becoming diaphoretic and began vomiting (28). In this case, there was no respiratory depression and naloxone was administered due to nausea and vomiting and as such cannot be used to assess the effects of this dose on respiratory status after 3 hours.
Previously work in relation to weight based dosing of ITM in the setting of spinal surgery has indicated that doses of 2-4mcg/kg (eg 75kg gives a range of 150-300mcg) yielded effective post-operative analgesia with minimal side effects and thus these patients could be managed at ward level (24). In this current study a mean dose of more than double this (8.12 ± 0.53mcg/kg) was administered which may account for the incidence of respiratory depression observed. The maximum dose administered in our study was 19.23mcg/kg which resulted in a minimum respiratory rate of 10 breaths per minute and the lowest respiratory rate observed in this study was 5 breathes per minute in a patient who received 10.71mcg/kg ITM. Both of these patients received only paracetamol as further analgesia in ICU. These doses are relatively high in comparison to much of the literature however this lack consistency in dose related responses echos that of much of the literature and as such may negate the use of a dose per weight approach to ITM administration
Incidence of respiratory depression has been shown to peak 8–10 hours after the application of ITM (29). This is the major overriding influence on the destination of these patients post-operatively. With the pressure on HDU/ICU beds and lack of continuous monitoring on the wards this leads to ward based care being the only available for post-operative care and the option of ITM administration is obviated.
The ASRA practice guidelines (2) recommends that the lowest efficacious dose of neuraxial opioids are administered as well as that all patients receiving neuraxial opioids should be monitored for adequacy of ventilation (e.g. respiratory rate, depth of respiration), oxygenation (e.g. pulse oximetry when appropriate) and level of consciousness. Previously there has been little consensus on the definition of respiratory depression. Ko et al. reviewed 96 studies of which forty-four did not define respiratory depression, despite referring to the state, and the subsequent studies used a range of parameters including respiratory rate, with or without the combination of arterial blood gas values and the use of naloxone (30).
For the purposes of this study we decided for practicality to use the Irish Health Service Executive (HSE) National Early Warning Score (INEWS) parameters as a scale of vital sign deterioration, including respiratory depression(31). In this standardised vital sign record sheet nursing staff are mandated to contact medical staff once certain parameters are met. For respiratory rate a value of ≤ 8 breaths per minute is considered to warrant an immediate medical review and as such this value was taken as our threshold definition of respiratory depression. Since the study was carried out a new early warning score system, INEWS V2(32), has been introduced which is identical apart from its addition of confusion to the AVPU scale (ACVPU: C = confusion). As such, results described herein may differ if the study was repeated with the revised INEWS parameters.
Early warning scores have been developed to facilitate early detection of deterioration by categorising a patient’s severity of illness and prompting nursing, and other healthcare professionals, to request a medical review at specific trigger points, utilising structured communication tools whilst following a definitive escalation plan. These are collated on the INEWS chart (Fig. 3).
In addition to this, the completion of neurological (e.g. Glasgow coma scale), intake-output etc. observations must be carried out whenever indicated with their own guidelines of escalation. The mean INEWS of 4.9 in our study group (after ITM doses of average 549mcg), requires INEWS escalation protocol (Fig. 4.) to be activated.
This confirms the potential need for continuous monitoring and 1 hourly observation similar to what is recommended by ASRA (2). With appropriate staff ratios, education and monitoring equipment this could potentially be provided on ward level. EWS of equal or more than seven requires nurse in charge and team Registrar or On-call Consultant, to be informed and immediately review the patient and applying continuous monitoring. The recommended response is that the reviewing doctor should consider activating Emergency Response System and plan transfer to higher level of care.
Establishing post-operative monitoring for patients after ITM doses of > 300mcg on general surgical wards will be challenging. The additional work load would require nursing and primary staff training and may benefit from the existence of an anaesthesiology led Acute Pain Service.
In the obstetric setting, ITM has been shown to provide better post LSCS analgesia than both patient controlled epidural analgesia (PCEA) and post LSCS epidural morphine bolus of 3mg (33). Within this field, more conservative doses of intrathecal morphine (up to 200mcg) are commonly used in elective and emergent caesarean section (CS) with post-operative monitoring occurring primarily at ward level without the requirement for escalation to HDU/ICU. In this cohort, evidence indicates that doses of 250-300mcg are safe in this setting without hypoventilation affecting patient care (34). That being said the consensus remains that these patients require continual monitoring for the 24 hours following ITM administration (35).
Evidently, the obstetric population is unique, without, in the most part, the common co-morbidities and age profile exhibited by the general surgical population. As such care must be taken with patients of higher ASA grade/APACHE Scores and as is current practice, post-operative destination must be influenced by the patients’ pre-operative condition. As was evidenced in this study patients presenting for surgery with higher ASA grade/APACHE II Score/co-morbidities would still necessitate the admission to ICU.
In the current study patient selection for intrathecal morphine administration and subsequent admission to HDU/ICU was influenced by bed occupancy, surgical procedure, emergent nature of the surgery and patients’ pre-operative condition.
As such patients’ of higher ASA grade were more commonly selected due to their perceived higher post-operative requirements and increased benefit from ITM versus intravenous opioid, with those deemed to have lower post operative requirements, in times of restricted HDU/ICU availability, being denied the analgesic effects due to lack of sufficient post-operative monitoring practices on general surgical wards. Be that as it may the patients here in would most likely required HDU/ICU admission postoperatively based on their higher ASA and subsequent higher APACHE scores. Restrictions to monitoring at ward level in the postoperative period, as well as the current application of the INEWS criteria and its implications, are obstacles to ward level care for these patients and as such curtails to use of this technique. If however these were overcome, by means of an acute pain team or similar services which would cater for the increased requirements of these patients and represent an added layer of care at ward level, patient selection would be paramount to its success. Elective procedures carried out on patients with lower ASA and APACHE would be most eligible. With the use of lower doses of ITM (≤ 300mcg) and the installation of an acute pain service at ward level to cater for these patients ward level roll out of post-operative care for ITM recipients could be possible.
The limited access to critical care beds locally (3), nationally (36) and internationally (37), creates many non-clinical challenges for the anaesthesiologists, surgeons and nursing staff. The lack of access to a critical care bed for scheduled or unscheduled surgery creates a demand-resource bottle neck and results in undue pressure on clinicians (38). Similar issues have previously been noted in relation to the administration of epidural analgesia (3) in our institution. Higher bed number and dedicated surgical beds, are potential solutions, however, in times of austerity the solution must be found in effective utilisation of existing infrastructure and human resources while concurrently improving standards of care. This may include change of practice and admission of selected patients, whom received > 300mcg of ITM, to general surgical wards.
The limitations of this study include the Small cohort analysed, the single-centred and retrospective nature of the study. The possibility of skewed outcomes due to selection criteria of patients as a result of ICU capacity issues also limit its interpretation.
In an effort to increase to extend the postoperative care of these patients past the doors of the ICU and onto the general wards in the hope of abolishing ICU capacity issues as a limiting factor in our ability to offer ITM to those who will benefit immensely from it, further work related to the postoperative INEWS scoring profile of patients administered with a lower dose of ITM (< 300mcg) would be of great benefit to elucidate the safe common ground between efficacy and acceptable side effect profile.