Blog with interesting cases and/or problems related to anesthesia with discussion based on best evidence in the literature.

November 14, 2018

26 year old on TPN for major bowel surgery

A 26 year old female with previous bowel surgery for superior mesenteric artery (SMA) syndrome, presents to have a revision of her gastrojejunal anastomossis.  SMA syndrome occurs when the aorta and superior mesenteric artery wrap around the duodenum in such a way as to compromise the passage of food through the narrowed part. The syndrome is often related to loss of the mesenteric fat pad in the area. In this case the patient suffered from anxiety and a history of anorexia nervosa likely leading to the loss of the mesenteric fat pad. During two previous abdominal surgeries the patient suffered complications of post operative pain unrelieved by post operative thoracic epidural analgesia and multimodal analgesia.  She was also persistently nauseous and struggled to tolerate food post op.  She had to return to the OR a second time due to the development of a stricture post op in her small intestine.  The second surgery also resulted in a similar challenge of pain control with severe nausea.  The patient is now scheduled for a third surgery, a revision gastrojejunal anastomosis and gastrojejunostomy.

Given that the patient is very likely to suffer as in her prior surgeries with significant pain, I have decided to consider an aggressive multimodal pain regimen for post op pain.  Currently, many surgeons are requesting transversus abdominal pain blocks (often with catheters) for post op pain control after abdominal surgery.  In many cases, it appears that this method of pain control is supplanting TEA as the primary regional technique for pain control after abdominal surgery.  Unfortunately, I have had less success with the TAP technique for open abdominal surgery in particular with upper (above the umbilicus) abdominal surgery.  It is well known that the transverses abdominal plane block (TAP) provides somatic analgesia to the skin and anterior abdominal wall. Unfortunately, pain sensation from the viscera and peritoneum are not blocked with this technique as it is with epidural analgesia (EA).  Recently a head to head trial comparing TAP vs EA was published [1].  The authors found that in lower abdominal surgery, TAP had similar pain control to EA patients for the first 16 hours.  After 16 hours up to 48 hours, the group with epidural analgesia had better pain control.  For incisions above the umbilicus, it is recommended that a subcostal technique be used.  However, for long incisions, it is often difficult to get enough spread of local anesthetic in the transversus abdominis plane to block all of the necessary nerves. Nevertheless, Rao et al. were able to show that after major abdominal surgery, TAP catheters were equal to EA in terms of pain scores, opioid requirements, and patient satisfaction [2]. In another study of open laparotomy patients (n=51)[3], Ganapathy et al. found that TAP catheters were essentially equivalent to EA during 72 hours in terms of pain control. However, in another study, TAP catheters were inferior to EA for pain control after major open abdominal surgery [4].  A small meta analysis of four studies was unable to find any significant differences in pain control or opioid use after abdominal surgery when comparing TAP catheters with EA [5].  However, there was a trend toward increased morphine use in the TAP catheter group.  All, in all, it would appear that  for abdominal surgery TAP catheters can be a reliable alternatively to EA when pain control is the only outcome of interest. However, multiple studies and a cochrane review have shown that for the important endpoint of reduction in post operative ileus, EA is helpful.  (see here for cochrane review). In this particular case, post operative ileus is a major concern.  The patient is currently on TPN, due to continued poor oral intake.  It will be imperative to maximize her chances of avoiding a prolonged post operative ileus.  Therefore,  EA would be an ideal choice.  However, this patient is likely to still have significant post operative pain as she did after her prior two abdominal surgeries despite having a functioning thoracic epidural.  There is evidence that in patients with difficult to treat pain, that ketamine can be helpful.  There is a large literature related to ketamine use in the perioperative period. In 2010, a Cochrane review found that sub-anesthetic ketamine reduced analgesic requirements and/or pain scores in 27 of 37 RCTs [10].  Currently, most guidelines suggest giving a bolus of 0.5 mg/kg at the beginning of the case plus an infusion of 0.25mg/kg/hr during surgery.   De Koch et al. found that intraoperative ketamine  ( 0.5 mg/kg bolus + 0.25 mg/kg/hr infusion) reduced morphine consumption in patients having abdominal surgery [6].  Importantly, this occurred even though all patients received aggressive EA.  Furthermore, they were able to show that secondary hyperalgesia was reduced in the ketamine group and that in this group, chronic post operative pain was significantly less at 6 months after surgery.  Himmeslseher et al. published a meta analysis on ketamine for post operative pain control.  They recommend ketamine to reduce post operative pain and provided the following recommendations:

Major surgery:  0.5 mg/kg bolus prior to incision and 0.5 mg/kg/hr infusion until end of surgery. then post op infusion of 0.12 mg/kg/hr x 24 hours in the post operative period.

Minor surgery: 0.25 mg/kg bolus prior to incision + 0.25 mg/kg/hr infusion until the end of surgery.

Dosages above are fairly aggressive, and it is clear that post operative hallucinations, vivid dreams and other cognitive affects are more frequent and more severe at higher doses.  Therefore, I tend to decrease the doses from those recommended above.

Multipmodal analgesia will be very important so I will given IV Tylenol during the surgery and then q 8 hours post op.

 Another option is an IV infusion of Magnesium.  Magnesium as an adjunct for pain control has been considered for decades.  A large number of clinical studies looking at the use of magnesium for post operative pain control have been published with mixed results.  A systematic review in 2007 that included 14 studies could not detect a beneficial effect of systemic magnesium administration on post operative pain control [8].  In 2013, another systematic review was undertaken and was able to demonstrate a beneficial effect of magnesium on pain control [9].  The largest improvement was the reduction in morphine consumption as noted in the figure below.  Most of the studies utilized a 30 mg/kg bolus or a 50 mg/kg bolus +/- an infusion of  between 8 mg/kg/hr to 15 mg/kg/hr intraoperatively or a few even post operatively.

Fig 1 post operative morphine consumption is reduced with magnesium.

Magnesium acts as an NMDA antagonist to reduce the perception and duration of pain.

Recently, more and more groups have started to take interest in the possibility of gabapentin reducing post operative pain and/or analgesic opioid requirements. In 2013, an article in Anesthesiology stated that the current evidence suggested that gabapentinoids (gabapentin and pregabalin) could reduce preoperative acute pain/analgesic requirements and the incidence of post surgical chronic pain development.

gabapentinoid pharmacology: these are not active at the GABA-a receptor although they are GABA structural analgues.

These GABA analogues actually bind to the alpha 2-delta subunit of pre synaptic P and Q type voltage gated calcium channels.  Doesn't make much sense, but that's how they cause the effect we are looking for. This is believed to modulate the release of excitatory neurotransmitter from activated nociceptors. So, by inhibiting Calcium induced release of glutamine, these agents can inhibit pain transmission and/or decrease central sensitization.  Alternatively, some evidence indicates that their antinociceptive mechanism may arise through activation of noradrenergic pain-inhibiting pathways in the spinal cord and brain. (see figure)

In 2016 a meta analysis of gabapentinoids [11] in dosages from 300 mg to 1200 mg found that they were helpful in reducing morphine consumption for the first 24 hours after surgery.  They did report increased sedation levels in patients who received gabapentinoids, and there was no decrease in side effects such as pruritus, nausea or vomiting.  Two different studies looked at gabapentin as a part of a multimodal analgesia program and both concluded that it was of questionable benefit in this context. The first of these two studies was a RCT in TKA with gabapentin [12].  In this study patients were given 600 mg gabapentin preop with 200 mg q8 hours post op along with morphine, ketorolac and tylenol.   Morphine consumption and VAS scores were similar between groups.  Monks et al. [13] looked at gabapentin in post cesarean section patients at dose of 600 mg preop and 200 mg q8 hours post op. Patients received spinal morphine. There was a very slight decrease in morphine consumption in the group receiving gabapentin and the authors concluded that gabapentin is of questionable benefit in cesarean section patients.  One consideration that is important is to understand that gabapentin is an oral medication and was not possible to use in our case in a patient requiring TPN due to an inability to tolerate oral intake.  In addition, I was planning an aggressive multimodal pain program to include regional anesthesia, toradol, tylenol IV, magnesium infusion and a ketamine infusion, thereby making gabapentin an unlikely success in further reducing post op pain scores or opioid consumption.
One day prior to the scheduled surgery the pre admissions testing nurse called me to report that the patient had a lab drawn and that her potassium was 2.9 mEq/L. The nurse at the PAT clinic reported that the patient had a PICC line where she receives TPN in addition to potassium replacement.  The nurse also revealed that the patient suffers from orthostatic hypotension for which she is prescribed midorine and fludrocortisone.  I instructed the nurse to call the patient and have her stop her fludrocortisone the day before surgery and to come in early for repeat K+ lab draw with an order to start 20 mEq of postassium if her K+ level was below 3.1 mEq/L.

Orthostatic hypotension is often caused by failure of the autonomic nervous system. There are a variety of reasons for failure of the autonomic nervous system including:

  • Multiple system atrophy
  • familial dysautonomia
  • dementia with lewy bodies
  • Shy-Drager's syndrome
  • Parkinson's disease
  • longstanding diabetes
  • Vitamin deficiencies (our patient)
  • Amyloidosis
  • Bronchogenic carcinoma
  • Pure autonomic failure
Treatment for othorstatic hypotension can include a direct vasocontrictor.  My patient was taking midodrine, which is a prodrug and acts on the alpha 1 adrenergic receptor to cause vasoconstriction. Unfortunutely, this can lead to supine hypertension that is severe in some patients. This supine hypertension can result in pressure natriuresis leading to a worsening of orthostatic hypotension.  In patients taking midodrine for autonomic failure, there is typically an associated denervation hypersensitivity making these patients exquisitely sensitive to norepinephrine.   Patients with autonomic failure have other clinical manifestations as well.  These may include post prandial hypotension, urinary bladder dysfunction leading to urinary retention, and decreased gastrointestinal motility.

Fludrocortison is a mineralocorticoid used in patients with orthostatic hypotension.  It results in fluid retention and patients often will gain 2 to 3 Kg of water weight before receiving full benefit of this medication. Fludrocortisone does have some  glucocorticoid activity above dosages of 0.3 mg per day and this must be considered as to whether the HPA axis may be inhibited.  Mineralocorticoids act by mimicking aldosterone (binding to the aldosterone receptor in the cell necleus) which causes sodium retention at the expense of excretion of potassium and hydrogen ions. The action occurs in the renal collecting tubules.   This can lead to severe hypokalemia and metabolic alkalosis.  In addition, about 10% of patients also suffer from hypomagnesemia with chronic fludrocortisone therapy.  Because fludrocortisone does have some glucocorticoid activity, I could not ensure that the patient's HPA axis was not suppressed, and therefore, in addition to 4 mg of dexamethosone (purely glucocorticoid activity) I gave a one time dose of solucortef 50 mg.  This medication has both glucocorticoid and mineralocorticoid activity. 

On the day of surgery the patient arrived and a repeat potassium level came back at 3.3 mEq/L. Therefore, KCL infusion was not required prior to proceeding as I was worried might happen.  As discussed above, there is evidence that EA and bilateral subcostal TAP catheters are equivalent.  It was decided to proceed with GETA and post operative placement of subcostal TAP catheters.  The patient weight was 50 kg.  The patient was given 2 mg of versed and 2 mg of dilaudid and we rolled to the OR.  Induction was with propofol and rococuronium.  The patient was given ketamine in 25 mg increments to a total of 100 mg.  She was given MgSO4 2 GM intraoperatively, and another 1 GM was infused post operatively.  She also received decadron 4 mg, solocortef (to add some mineralocorticoid activity) 50 mg, IV tyelonol 1000mg, and zofran 4 mg.  The open laparotomy with revision of gastrojejunal anastomosis was uneventful and the patient arrived in the PACU extubated and breathing comfortably.  After 30 min the patient was interviewed and complained of 8/10 pain.  The nurse administered opioid pain medications.  A post operative ketamine infusion was begun at 5 mg/hr with a magnesium infusion of 250 mg/hr.  She received an additional amount of magnesium in her TPN solution.  The surgeon also prescribed a PCA with hydromorphone.  On POD 1, the patient appeared comfortable in her bed but complained of 8/10 pain.  It should be noted that on the first night on the day of surgery, the nurses called me to tell me that the patient had respiratory depression and that they had d/c'd all of her pain medications until she woke up.  It was decided to restart her magnesium and ketamine infusion, and cut her hydromorphone dose in half.  The patient requested EA, however, the surgeon intervened to avoid this.  The patients was NPO and therefore, not receiving fludrocortisone or midodrine, both oral medications.  Her blood pressures were low normal.

In this case, EA is likely to have been a better choice than TAP catheters.  Particularly on POD 1 when it became apparent that the patient had an event of respiratory depression from opioids requiring adjustment of the medication.  In addition, the patient perceived that her pain control was not adequate nor being addressed.  She stated that the TAP catheters were not working.  A test with ice to the skin around the incision was unable to detect any decrease in sensation or perception of cold.  This is a fairly good indicator of failure of block.  I have a long experience with the placement of TAP catheters and doing the subcostal block.  This patient was thin, and the US guided block went flawless, with excellent landmarks that were well visualized. However, the subcostal approach relies on local anesthetic spreading throughout the transversus abdominis plane and finding the nerves as they run along to their destination.  The actual nerves are not visualized and it is impossible to guarantee that all of the nerves will be bathed in local anesthetic (LA).  This is also true for EA, however.  The patient did state that the block was patchy.  To me this indicated that indeed the LA was located around several nerves, but that there were others not reached by the LA. This, to me constitutes a general weakness of the TAP approach than my technique.  On POD 2 the patient appeared much more comfortable and in fact had reduced the amount of opioid pain medication she was consuming.

1. Sadasivan Shankar Iyer, Harshit Bavishi, Chadalavada Venkataram Mohan, and  Navdeep Kaur,  Anesth Essays Res. 2017 (11)7: 670-675

2. Rao Kadam V, Van Wijk RM, Moran JI, Miller D. Anaesth Intensive Care. 2013;41:476–81.

3. Ganapathy S, Sondekoppam RV, Terlecki M, et al. Eur J Anaesthesiol 2015;32:797–804

4. Wahba SS, Kamal SM. J Anesth 2014;28:517–23.

5. Zhang P, Deng XQ, Zhang R, Zhu T.  Br J Anaesth. 2015;114:339. 

6.  De Kock M, Lavand'homme P, Waterloos H.  Pain 92(2001) 373-380.

7. Himmeslseher S, durieux ME. Ketamine for perioperative Pain Management. Anesthesiology. 2005; (102):211-20.

8.  Lysakowski, C, Dumont, L, Czarnetzki, C, Tramèr, MR . Anesth Analg. (2007). 104 1532–9 

9Gildasio S. De Oliveira, Jr, M.D., M.S.C.I.Lucas J. Castro-Alves, M.D.Jamil H. Khan, B.S.Robert J. McCarthy, Pharm.D. Anesthesiology 07 2013, Vol.119, 178-190

10. Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2006

11. Sudha Arumugam, Christine SM Lau, and  Ronald S ChamberlainJ Pain Res. 2016; 9: 631–640.

12. Paul JE, Nantha-Aree M, Buckley N, Cheng J, Thabane L, Tidy A, DeBeer J, Winemaker M, Wismer D, Punthake D, Avram V; Gabapentin does not improve multimodal analgesia outcomes for total knee arthroplasty: a randomized controlled trial; Canadian Journal of Anesthesia 2013, 60:423-431

13. Monks DT, Hoppe DW, Downey K, Shah V, Bernstein P, Carvalho JCA; A perioperative dose of gabapentin does not produce a clinically meaningful improvement is analgesia after cesarean delivery; Anesthesiology 2015 August, 123(2): 320-326

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