Acute pain in sickle cell disease (SCD) involves multiple, complex downstream effects of vaso-occlusion, ischemia, and inflammation, ultimately resulting in severe and sudden pain. Historically, opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) have been the cornerstone of treatment for acute SCD pain. However, given the evolving understanding of the complexity of pain pathways in SCD and the desire to avoid NSAID and opioid-induced side effects, a multimodal approach is needed to effectively treat acute SCD pain. In this article we review recent research supporting the utilization of nonopioid pharmacologic interventions and nonpharmacologic interventions while also describing the research questions that remain surrounding their use and efficacy and effectiveness in the management of acute SCD pain. Furthermore, we review care delivery processes shown to improve acute SCD pain outcomes and highlight areas where more work is needed. Through this comprehensive approach, alternative mechanistic pathways may be addressed, leading to improved SCD pain outcomes.

1.
Yusuf
HR
,
Atrash
HK
,
Grosse
SD
,
Parker
CS
,
Grant
AM
.
Emergency department visits made by patients with sickle cell disease: a descriptive study, 1999-2007
.
Am J Prev Med
.
2010
;
38
(
suppl 4
):
S536
-
S541
.
2.
Moerdler
S
,
Manwani
D.
New insights into the pathophysiology and development of novel therapies for sickle cell disease
.
Hematology Am Soc Hematol Educ Program
.
2018
;
2018
(
1
):
493
-
506
.
3.
National Heart, Lung, and Blood Institute
.
Evidence-based management of sickle cell disease: expert panel report
.
September
2014
. Accessed
August
8
,
2024
. https://www.nhlbi.nih.gov/health-topics/evidence-based-management-sickle-cell-disease.
4.
Brandow
AM
,
Carroll
CP
,
Creary
S
, et al.
American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain
.
Blood Adv
.
2020
;
4
(
12
):
2656
-
2701
.
5.
Bell
RF
,
Kalso
EA
.
Ketamine for pain management
.
Pain Rep
.
2018
;
3
(
5
):
e674
.
6.
Laulin
JP
,
Maurette
P
,
Corcuff
JB
,
Rivat
C
,
Chauvin
M
,
Simonnet
G.
The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance
.
Anesth Analg
.
2002
;
94
(
5
):
1263
-
1269
.
7.
Yu
H
,
Chen
A
,
Chen
E
,
Long
LS
,
Agrawal
AK
.
Low-dose ketamine infusion for pediatric hematology/oncology patients: case series and literature review
.
J Pediatr Hematol Oncol
.
2022
;
44
(
1
):
e188
-
e193
.
8.
Harris
EM
,
Vilk
E
,
Heeney
MM
,
Solodiuk
J
,
Greco
C
,
Archer
NM
.
A systematic review of ketamine for the management of vaso-occlusive pain in sickle cell disease
.
Pediatr Blood Cancer
.
2021
;
68
(
7
):
e28989
.
9.
Schwenk
ES
,
Viscusi
ER
,
Buvanendran
A
, et al.
Consensus guidelines on the use of intravenous ketamine infusions for acute pain management from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists
.
Reg Anesth Pain Med
.
2018
;
43
(
5
):
456
-
466
.
10.
Alshahrani
MS
,
Alghamdi
MA
.
Ketamine for sickle cell vaso-occlusive crises: a systematic review
.
Saudi J Med Med Sci
.
2021
;
9
(
1
):
3
-
9
.
11.
Lubega
FA
,
DeSilva
MS
,
Munube
D
, et al.
Low dose ketamine versus morphine for acute severe vaso occlusive pain in children: a randomized controlled trial
.
Scand J Pain
.
2018
;
18
(
1
):
19
-
27
.
12.
Alshahrani
MS
,
AlSulaibikh
AH
,
ElTahan
MR
, et al
;
GUIDE Group
.
Ketamine administration for acute painful sickle cell crisis: a randomized controlled trial
.
Acad Emerg Med
.
2022
;
29
(
2
):
150
-
158
.
13.
Kim
M
,
Cho
S
,
Lee
JH
.
The effects of long-term ketamine treatment on cognitive function in complex regional pain syndrome: a preliminary study
.
Pain Med
.
2016
;
17
(
8
):
1447
-
1451
.
14.
Nguyen
NL
,
Kome
AM
,
Lowe
DK
,
Coyne
P
,
Hawks
KG
.
Intravenous lidocaine as an adjuvant for pain associated with sickle cell disease
.
J Pain Palliat Care Pharmacother
.
2015
;
29
(
4
):
359
-
364
.
15.
Zavala
NA
,
Knoebel
RW
,
Anitescu
M.
Lidocaine and ketamine infusions as adjunctive pain management therapy: a retrospective analysis of clinical outcomes in hospitalized patients admitted for pain related to sickle cell disease
.
Front Pain Res (Lausanne)
.
4
August
2022
;
3
:
878985
.
16.
Puri
L
,
Morgan
KJ
,
Anghelescu
DL
.
Ketamine and lidocaine infusions decrease opioid consumption during vaso-occlusive crisis in adolescents with sickle cell disease
.
Curr Opin Support Palliat Care
.
2019
;
13
(
4
):
402
-
407
.
17.
Anghelescu
DL
,
Morgan
KJ
,
Frett
MJ
, et al.
Lidocaine infusions and reduced opioid consumption-retrospective experience in pediatric hematology and oncology patients with refractory pain
.
Pediatr Blood Cancer
.
2021
;
68
(
11
):
e29215
.
18.
Rizvi
MB
,
Kessler
DO
,
Rabiner
JE
.
Role of regional anesthesia in patients with acute sickle cell pain: a scoping review
.
Pediatr Blood Cancer
.
2023
;
70
(
1
):
e30063
.
19.
New
T
,
Venable
C
,
Fraser
L
, et al.
Management of refractory pain in hospitalized adolescents with sickle cell disease: changing from intravenous opioids to continuous infusion epidural analgesia
.
J Pediatr Hematol Oncol
.
2014
;
36
(
6
):
e398
-
e402
.
20.
Yaster
M
,
Tobin
JR
,
Billett
C
,
Casella
JF
,
Dover
G.
Epidural analgesia in the management of severe vaso-occlusive sickle cell crisis
.
Pediatrics
.
1994
;
93
(
2
):
310
-
315
.
21.
Karsenty
C
,
Tubman
VN
,
Liu
CJ
,
Fasipe
T
,
Wyatt
KEK
.
Regional anesthesia for sickle cell disease vaso-occlusive crisis: a single-center case series
.
Pediatr Blood Cancer
.
2022
;
69
(
6
):
e29695
.
22.
Rollé
A
,
Vidal
E
,
Laguette
P
, et al.
Pain control for sickle cell crisis, a novel approach? A retrospective study
.
Medicina (Kaunas)
.
2023
;
59
(
12
):
2196
.
23.
Heffler
MA
,
Brant
JA
,
Singh
A
, et al.
Ultrasound-guided regional anesthesia of the femoral nerve in the pediatric emergency department
.
Pediatr Emerg Care
.
2023
;
39
(
2
):
e30
-
e34
.
24.
Ibitoye
BM
,
Garrett
B
,
Ranger
M
,
Stinson
J.
Non-pharmacological pain interventions for sickle cell crisis in pediatrics: a scoping review
.
J Pediatr Nurs
.
July-August
2023
;
71
:
42
-
54
.
25.
Dev
P
,
Bavli
N
,
Sims
B
, et al.
Mindfulness and yoga therapy for acute pain in sickle cell disease
.
EJHaem
.
2024
;
5
(
1
):
131
-
135
.
26.
Rodgers-Melnick
SN
,
Bartolovich
M
,
Desai
NJ
, et al.
Massage therapy for children, adolescents, and young adults: clinical delivery and effectiveness in hematology and oncology
.
Pediatr Blood Cancer
.
2023
;
70
(
4
):
e30243
.
27.
Reece-Stremtan
S
,
Mahmood
L
,
Margulies
S
, et al.
Acupuncture as an adjunctive treatment for pain in hospitalized children with sickle cell disease
.
J Pain Symptom Manage
.
2021
;
62
(
6
):
1239
-
1244
.
28.
Tsai
SL
,
Bombacie
M
,
Licursi
M
,
Qian
Y
,
Stiles
GM
,
Lee
MT
.
Acupuncture for pediatric sickle cell pain management: a promising non-opioid therapy
.
Complement Ther Med
.
March
2020
;
49
:
102314
.
29.
Wihak
T
,
Burns
M
,
Miranda
J
,
Windmueller
G
,
Oakley
C
,
Coakley
R.
Development and feasibility testing of the comfort ability program for sickle cell pain: a patient-informed, video-based pain management intervention for adolescents with sickle cell disease
.
Clin. Pract. Pediatr. Psychol
.
2020
;
8
(
2
):
150
-
163
.
30.
Lin
JG
,
Kotha
P
,
Chen
YH
.
Understandings of acupuncture application and mechanisms
.
Am J Transl Res
.
2022
;
14
(
3
):
1469
-
1481
.
31.
Brousseau
DC
,
Alpern
ER
,
Chamberlain
JM
, et al
;
Pediatric Emergency Care Applied Research Network (PECARN)
.
A multiyear cross-sectional study of guideline adherence for the timeliness of opioid administration in children with sickle cell pain crisis
.
Ann Emerg Med
.
2020
;
76
(
3S
):
S6
-
S11
.
32.
Welch-Coltrane
JL
,
Wachnik
AA
,
Adams
MCB
, et al.
Implementation of individualized pain care plans decreases length of stay and hospital admission rates for high utilizing adults with sickle cell disease
.
Pain Med
.
2021
;
22
(
8
):
1743
-
1752
.
33.
Ojo
AS
,
Odipe
OG
,
Owoseni
O.
Improving the emergency department management of sickle cell vaso-occlusive pain crisis: the role and options of sublingual and intranasally administered analgesia
.
J Clin Med Res
.
2023
;
15
(
1
):
10
-
22
.
34.
Molokie
RE
,
Montminy
C
,
Dionisio
C
, et al.
Opioid doses and acute care utilization outcomes for adults with sickle cell disease: ED versus acute care unit
.
Am J Emerg Med
.
2018
;
36
(
1
):
88
-
92
.
35.
Tanabe
P
,
Silva
S
,
Bosworth
HB
, et al.
A randomized controlled trial comparing two vaso-occlusive episode (VOE) protocols in sickle cell disease (SCD)
.
Am J Hematol
.
2018
;
93
(
2
):
159
-
168
.
36.
Della-Moretta
S
,
Delatore
L
,
Purcell
M
, et al.
The effect of use of individualized pain plans in sickle cell patients presenting to the emergency department
.
Ann Emerg Med
.
2020
;
76
(
3S
):
S21
-
S27
.
37.
Carullo
V
,
Morrone
K
,
Weiss
M
, et al.
Demand-only patient-controlled analgesia for treatment of acute vaso-occlusive pain in sickle cell disease
.
Pediatr Blood Cancer
.
2022
;
69
(
8
):
e29665
.
38.
Harris
KM
,
Preiss
L
,
Varughese
T
, et al
;
Sickle Cell Disease Implementation Consortium
.
Examining mental health, education, employment, and pain in sickle cell disease
.
JAMA Netw Open
.
2023
;
6
(
5
):
e2314070
.
39.
Center to Advance Palliative Care
.
About palliative care
. Accessed
August
7
,
2024
. https://www.capc.org/about/palliative-care/.
40.
Bartholomew
F
,
De Castro
LM
.
Advance care planning in adults with sickle cell disease (SCD)
.
Blood
.
2010
;
116
(
21
):
391
.
41.
Nwogu-Onyemkpa
E
,
Dongarwar
D
,
Salihu
HM
, et al.
Inpatient palliative care use by patients with sickle cell disease: a retrospective cross- sectional study
.
BMJ Open
.
2022
;
12
(
8
):
e057361
.
You do not currently have access to this content.